USMLE WORLD STEP 1 Question List Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No:

Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Pulmonology Endocrinology Renal Reproductive system Pulmonology Head and neck Head and neck Neurology Hematology Endocrinology Neurology Head and neck Cardiology Renal Cardiology Pulmonology Head and neck Cardiology Head and neck Reproductive system Oncology Neurology Head and neck Musculoskeletal Genitourinary Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: Genetics Q No: 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50

GENETICS

Musculoskeletal Dermatology Hematology Gastrointestinal system Pulmonology Dermatology Endocrinology Neurology Neurology Musculoskeletal Neurology Neurology Gastrointestinal system Neurology Neurology Cardiology Hepatobiliary system Hematology Hematology Reproductive system Neurology Neurology Head and neck Head and neck Hematology

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GENETICS

Q NO 1: S!ienti$t$ %e:elo/ a te!hni6ue that /ro"ote$ intra!ellular #ol%in. an% .ly!o$ylation o# an a&nor"al tran$"e"&rane /rotein that 0oul% other0i$e &e %e.ra%e% &e#ore rea!hin. the !ell $ur#a!e. Thi$ te!hni6ue 0oul% &e "o$t hel/#ul in treatin. /atient$ 0ith= Phenylketonuria . Si!kle !ell ane"ia C. Mar#an $yn%ro"e D. Cy$ti! #i&ro$i$ E. 're%eri!k($ ata)ia

A.

Explanation: *'+,- i$ the "o$t !o""on CETR .ene "utation in /atient$ 0ith !y$ti! #i&ro$i$ 1CE2. Thi$ "utation %elete$ the three nu!leoti%e$ that !o%e #or /henylalanine at a"ino a!i% /o$ition +,-. *'+,- i$ the "utation re$/on$i&le in a//ro)i"ately 3,4 o# C' !a$e$ %ia.no$e% 0orl%0i%e. The CETR .ene !o%e$ #or the !y$ti! #i&ro$i$ tran$"e"&rane re.ulator 1CETR2 /rotein5 an inte.ral "e"&rane /rotein. The *'+,- "utation !au$e$ a&nor"al /rotein #ol%in. an% #ailure o# .ly!o$ylation. The CRTR /rotein i$ %e.ra%e% &e#ore it rea!he$ the !ell $ur#a!e5 !au$in. it$ !o"/lete a&$en!e #ro" the a/i!al "e"&rane o# e)o!rine %u!tal e/ithelial !ell$. The "ole!ular te!hni6ue %e$!ri&e% in thi$ 6ue$tion !oul% hel/ C' /atient$ &y re$torin. C'TR /rotein$ to the "e"&rane. 1Choi!e A2 Phenylketonuria re$ult$ #ro" "utation$ in the he/ato!yte intra!ellular en7y"e /henylalanine hy%ro)yla$e. The re$ult i$ /rotein "i$#ol%in.. Thi$ en7y"e i$ not nor"ally tran$/orte% to the !ell $ur#a!e. 1Choi!e 2 Si!kle !ell ane"ia re$ult$ #ro" "utation$ in the 89.lo&in .ene o# he"o.lo&in S. Thi$ /rotein i$ not a tran$"e"&rane /rotein. 1Choi!e C2 Mar#an $yn%ro"e re$ult$ #ro" an inherite% %e#e!t in the e)tra!ellular .ly!o/rotein5 #i&rillin91. 'i&rillin91 i$ not an inte.ral tran$"e"&rane /rotein. The a&nor"al #i&rillin91 "ono"er$ %i$ru/t#i&rillin91 /oly"eri7ation an% /re:ent the nor"al #or"ation o# "i!ro#i&ril$ in inter$titial !onne!ti:e ti$$ue. 1Choi!e E2 In 're%eri!k($ ata)ia5 the #rata)in .ene5 0hi!h !o%e$ #or a "ito!hon%rial /rotein i"/ortant in re$/iratory #un!tion an% iron ho"eo$ta$i$5 i$ "utate%. ;ere5 a GAA re/eat %i$ru/t$ tran$!ri/tion5 not /o$t9tran$lational /ro!e$$in.. E%u!ational O&<e!ti:e= In "o$t !a$e$ o# C'5 the "utation in the C'TR .ene /ro%u!t !au$e$ %e#e!ti:e /o$t9 tran$lational #ol%in. an% .ly!o$ylation. The re$ult i$ %e.ra%ation o# the CETR inte.ral "e"&rane /rotein &e#ore it rea!he$ the !ell $ur#a!e.

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GENETICS A. Short

Q NO 2: A 1+9year9ol% /atient i$ re#erre% to your o##i!e &y a tea!her 0ho i$ !on!erne% a&out the /atient($ learnin. a&ilitie$. A#ter e:aluatin. the /atient5 you %ia.no$e "il% "ental retar%ation. Cyto.eneti! $tu%ie$ o# the /atient($ &u!!al "u!o$al !ell$ re:eal a >3 ??@ karyoty/e. 'urther e:aluation i$ likely to re:eal= $tature5 &roa% !he$t5 a"enorrhea . Tall $tature5 .yne!o"a$tia5 in#ertility C. Ma!roor!hi%i$"5 lar.e <a0 an% ear$ D. Ara!hno%a!tyly5 $!olio$i$5 aorti! root %ilation E. Short $tature5 hy/otonia5 o&e$ity

Explanation: The >3 ??@ karyoty/e i$ %ia.no$ti! o# Aline#elter $yn%ro"e. The e)tra $e) !hro"o$o"e i$ a!6uire% %ue to B"eioti! non%i$<un!tionC %urin. .a"eto.ene$i$. Dariant$ in!lu%e >- ???@ an% >E ?@F>E ??@ "o$ai!i$". Neonate$ are /heno ty/i!ally nor"al. Si.n$ %o not &e!o"e e:i%ent until /u&erty. The "a<or #eature$ o# thi$ %i$or%er are %e$!ri&e% &elo0= 1. Aline#elter $yn%ro"e !au$e$ /ri"ary te$ti!ular #ailure %ue to hyalini7ation an% #i&ro$i$ o# the $e"ini#erou$ tu&ule$ an% the $u&$e6uent la!k o# te$to$terone $ynthe$i$. The te$te$ are $"all an% #ir". The$e a&nor"alitie$ re$ult in oli.oFa7oo$/er"ia5 in#ertility5 an% a&$en!e o# $e!on%ary $e) !hara!teri$ti!$. Gona%otro/in 1'S;I L;2 le:el$ are in!rea$e%5 an% the te$to$terone !on!entration i$ lo0. G. Te$to$terone %e#i!ien!y al$o lea%$ to the !hara!teri$ti! eunu!hoi% &o%y ha&itu$. Patient$ ha:e tall $tature an% .yne!o"a$tia. 'a!ial an% &o%y hair i$ a&$ent an% "u$!le "a$$ i$ %e!rea$e%. H. Co.niti:e $y"/to"$= Mil% "ental retar%ation i$ $een in $o"e /atient$5 thou.h the "a<ority ha$ nor"al intelli.en!e. The ri$k an% $e:erity o# "ental retar%ation in!rea$e$ 0ith ea!h a%%itional ? !hro"o$o"e. 1Choi!e A2 Patient$ 0ith Turner($ $yn%ro"e ha:e $hort $tature5 &roa% !he$t5 an% /ri"ary a"enorrhea. Only #e"ale$ are a##e!te%. Mo$t o# the /atient$ ha:e the karyoty/e >+ ?O5 thou.h $o"e are >+ ?,F>E ?? "o$ai!$. 1Choi!e C2 Ma!roor!hi%i$"5 lar.e <a0 an% "ental retar%ation are $een in /atient$ 0ith #ra.ile ? $yn%ro"e5 a !o""on !au$e o# here%itary "ental retar%ation5 inherite% a$ an ?9linke% trait. 1Choi!e D2 Ara!hno%a!tyly5 $!olio$i$ an% aorti! root %ilation are $i.n$ o# Mar#an $yn%ro"e5 0hi!h o!!ur$ %ue to an inherite% %e#e!t o# the e)tra!ellular "atri) /rotein #i&rillin. 1Choi!e E2 Patient$ 0ith Pra%er9Willi $yn%ro"e ha:e $hort $tature5 hy/otonia an% o&e$ity. Thi$ $yn%ro"e o!!ur$ %ue to a "i!ro %eletion on !hro"o$o"e 1+ that i$ inherite% #ro" the #ather. Patient$ are "entally retar%e%. E%u!ational O&<e!ti:e= >3 ??@ i$ the "o$t !o""on karyoty/e /ro%u!in. Aline#elter $yn%ro"e. Patient$ /re$ent 0ith tall $tature5 $"all #ir" te$te$5 a7oo$/er"ia an% .yne!o"a$tia. Mil% "ental retar%ation "ay &e /re$ent.

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GENETICS

Q NO 3: ilateral renal "a$$e$ !o"/o$e% o# #at5 $"ooth "u$!le an% &loo% :e$$el$ are %ete!te% in a youn. Cau!a$ian 0o"an. The /atient i$ "o$t likely to $u##er #ro"= A. rain ha"arto"a$ an% a$h9lea# $kin /at!he$ . Multi/le /eri/heral neuro #i&ro"a$ an% !a#I au lait $kin $/ot$ C. ilateral a!ou$ti! neuro"a$ D. Cere&ellar he"an.io"a$ an% li:er !y$t$ E. Ca/illary an.io"a$ o# the #a!e an% !horoi% '. Multi/le telan.ie!ta$ia$ o# the $kin an% "u!o$a Explanation: Renal an.io"yoli/o"a i$ a &eni.n tu"or !o"/o$e% o# &loo% :e$$el$5 $"ooth "u$!le5 an% #at 1an.io9"yo9li/o"a2. The$e tu"or$ !an &e %ia.no$e% 0ith an a&%o"inal CT $!an5 a$ the %en$ity o# #at i$ le$$ than that o# 0ater. An.io"yoli/o"a$ are a$$o!iate% 0ith tu&erou$ $!lero$i$. In /atient$ 0ith &ilateral renal an.io"yoli/o"a$5 the in!i%en!e o# tu&erou$ $!lero$i$ i$ -,9J,4. Tu&erou$ $!lero$i$ i$ an auto$o"al %o"inant !on%ition !hara!teri7e% &y !orti!al tu&er$ an% $u&e/en%y"al ha"arto"a$ in the &rain5 0ith !on$e6uent $ei7ure$ an% "ental retar%ation. Car%ia! rha&%o"yo"a$5 #a!ial an.io#i&ro"a$5 an% leat9$ha/e% /at!he$ o# $kin la!kin. /i."ent 1a$h lea# /at!he$2 !an o!!ur in thi$ !on%ition a$ 0ell.

1Choi!e 2 Neuro#i&ro"ato$i$ Ty/e 1 i$ an auto$o"al %o"inant %i$or%er !hara!teri7e% &y neuro#i&ro"a$ 1/le)i#or" an% $olitary25 o/ti! .lio"a$5 /i."ente% no%ule$ o# the iri$ 1Li$!h no%ule$25 an% !utaneou$ hy/er/i."ente% "a!ule$ 1!a#I au lait $/ot$2.

1Choi!e C2 Neuro#i&ro"ato$i$ Ty/e G i$ an auto$o"al %o"inant %i$or%er "arke% &y &ilateral a!ou$ti! neuro"a$. The$e /atient$ "ay al$o %e:elo/ "ulti/le "enin.io"a$5 .lio"a$5 an% e/en%y"o"a$ o# the $/inal !or%. 1Choi!e D2 Cere&ellar he"an.io"a$ an% li:er !y$t$ are $een in Don ;i//el9Lin%au Di$ea$e5 an auto$o"al %o"inant !on%ition. The$e /atient$ are at hi.h ri$k #or &ilateral renal !ell !ar!ino"a$. 1Choi!e E2 Stur.e9We&er $yn%ro"e 1SDDS2 i$ a rare !on.enital :a$!ular %i$or%er !hara!teri7e% &y a #a!ial /ort90ine $tain an% a le/to"enin.eal an.io"a. 1Choi!e '2 Patient$ 0ith here%itary he"orrha.i! telan.ie!ta$ia 1al$o !alle% O$ler9 Ren%u9We&er $yn%ro"e2 %e:elo/ "ulti/le telan.ie!ta$ia$ o# the $kin an% "u!o$a. The ty/i!al /re$entation i$ re!urrent e/i$ta)i$ or .a$trointe$tinal &lee%in. 1"elena2. E%u!ational O&<e!ti:e= Renal an.io"yoli/o"a i$ a &eni.n tu"or !o"/o$e% o# &loo% :e$$el$5 $"ooth "u$!le5 an% #at. ilateral renal an.io"yoli/o"a$ are a$$o!iate% 0ith tu&erou$ $!lero$i$5 an auto$o"al %o"inant !on%ition.

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GENETICS

Q NO 4: A 139year9ol% Cau!a$ian #e"ale ha$ ne:er ha% "en$trual &lee%in.. She i$ 1>- !" tall5 0ei.h$ >H k. 1J>.3 l&25 an% ha$ /oorly %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$. On /el:i! ultra$oun%5 her o:arie$ are $"all an% elon.ate%. Whi!h o# the #ollo0in. i$ the "o$t likely !au$e o# thi$ /atient($ !on%itionK A. Mitoti! error in early %e:elo/"ent . Trinu!leoti%e re/eat e)/an$ion C. Uni /arental %i$o"y D. alan!e% re!i/ro!al tran$lo!ation E. 'ra"e$hi#t "utation Explanation: Thi$ /atient a//ear$ to ha:e Turner $yn%ro"e5 a !on%ition that o!!ur$ in a//ro)i"ately 1 in G,,, li:e&orn #e"ale$ 1an% in 1+4 o# all $/ontaneou$ a&ortion$2. Clini!al "ani#e$tation$ o# Turner $yn%ro"e in!lu%e the a&nor"alitie$ li$te% &elo0. 1. Phenoty/i! a&nor"alitie$= Short $tature5 0e&&e% ne!k5 hi.h /alate5 lo0 /o$terior hair line5 B$hiel%C !he$t5 0i%ely9$/a!e% ni//le$5 $hort #ourth "eta!ar/al G. Uro.enital a&nor"alitie$= /ri"a a"enorrhea5 un%er%e:elo/e% B$treakC o:arie$5 %e!rea$e% e$tro.en an% in!rea$e% .ona%otro/in$5 a&$ent $e!on%ary $e) !hara!teri$ti!$5 hor$e$hoe ki%ney H. Car%ia! a&nor"alitie$= !oar!tation o# the aorta5 &i!u$/i% aorti! :al:e >. Ly"/hati! a&nor"alitie$= e%e"a o# e)tre"itie$ in neonate$5 !y$ti! hy.ro"a$ Turner $yn%ro"e i$ .eneti!ally hetero.eneou$. The !la$$i! :ariant o# !o"/lete "ono$o"y 1>+5 ?O2 o!!ur$ in a "inority o# Turner $yn%ro"e /atient$5 0ith "o$t %e"on$tratin. "o$ai!i$". In the "o$ai! /o/ulation5 one .eneti! line !ontain$ !ell$ 0ith a nor"al nu"&er o# !hro"o$o"e$ 1>E ??25 0hile the other .eneti! line !ontain$ !ell$ that are "ono$o"i! 1>+5 ?O2. oth line$ ori.inate #ro" a $in.le 7y.ote. While tri$o"ie$ an% non"o$ai! "ono$o"ie$ ty/i!ally re$ult #ro" "eioti! non%i$<un!tion5 "o$ai!i$" ari$e$ $e!on%ary to "itoti! error$ a#ter #ertili7ation ha$ taken /la!e. So"e in%i:i%ual$ 0ith Turner $yn%ro"e ha:e nor"al karyoty/e$ 1>E ??2 0ith /artial %eletion o# one or "ore ar"$ o# the ? !hro"o$o"e. Thi$ %e#e!t i$ ter"e% B/artial "ono$o"yC an% i$ a$$o!iate% 0ith the $tan%ar% !lini!al "ani#e$tation$ o# Turner $yn%ro"e. 1Choi!e 2 Trinu!leoti%e re/eat e)/an$ion i$ re$/on$i&le #or nu"erou$ %i$ea$e$5 in!lu%in. #ra.ile ? $yn%ro"e 1CGG re/eat$25 "yotoni! %y$tro/hy 1CTG re/eat$25 an% ;untin.ton %i$ea$e 1CAG re/eat$2. 1Choi!e C2 Uni/arental %i$o"y o!!ur$ 0hen an in%i:i%ual inherit$ t0o !o/ie$ o# a !hro"o$o"e #ro" one /arent an% no !o/ie$ o# the !hro"o$o"e #ro" the other /arent. Pra%er9Willi $yn%ro"e o!!ur$ in tho$e 0ho ha:e t0o "aternal !o/ie$ o# !hro"o$o"e 1+ 1"aternal uni/arental %i$o"y2 an% An.el"an $yn%ro"e o!!ur$ in tho$e 0ho ha:e t0o /aternal !o/ie$ o# !hro"o$o"e 1+ 1/aternal uni/arental %i$o"y2. Uni/arental %i$o"y i$ not a$$o!iate% 0ith Turner $yn%ro"e. 1Choi!e D2 In &alan!e% #or"5 a re!i/ro!al 1' ro&ert$onian2 tran$lo!ation i$ !lini!ally $ilent &e!au$e there i$ no e)!e$$ or $horta.e o# .eneti! "aterial. An un&alan!e% tri$o"y G1 1in 0hi!h one !hro"o$o"e 1> !ontain$ the lon. ar"$ o# &oth !hro"o$o"e$ 1> an% G12 i$ re$/on$i&le #or H9>4 o# !a$e$ o# Do0n $yn%ro"e. 1Choi!e E2 A #ra"e$hi#t "utation i$ a .eneti! "utation in 0hi!h a nu"&er o# nu!leoti%e$ not %i:i$i&le &y three i$ in$erte% or re"o:e% #ro" the DNA $e6uen!e. A$ a re$ult5 the rea%in. #ra"e i$ %i$ru/te% an% the /ro%u!t o# tran$lation i$ !han.e%. 'a"ilial hy/er!hole$terole"ia ha$ &een a$$o!iate% 0ith #ra"e$hi#t "utation$.

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GENETICS

E%u!ational O&<e!ti:e= Patient$ 0ith Turner $yn%ro"e "ay ha:e karyoty/e >+5 ?O 1!o"/lete "ono$o"y25 >+?,F>E?? 1"o$ai!i$"25 or >E?? 10ith /artial %eletion o# one ? !hro"o$o"e2. Mo$ai!i$" a//ear$ to a!!ount #or a "a<ority o# !a$e$ o# Turner $yn%ro"e.

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GENETICS

Q NO 5: A youn. !ou/le /re$ent$ to your o##i!e $eekin. /renatal !oun$elin.. The hu$&an% $u##er$ #ro" !y$ti! #i&ro$i$ an% i$ :ery !on!erne% that hi$ !hil% 0ill$ in her it the %i$ea$e. The #a"ily /e%i.ree i$ %ia.ra""e% &elo0 0ith the un&orn !hil% "arke% &y a re% arro0. What i$ the !han!e that thi$ !hil% 0ill inherit !y$ti! #i&ro$i$K A. 1F1E . 1FC. 1F> D. 1FH E. GFH '. HF> Explanation: Cy$ti! #i&ro$i$ re$ult$ #ro" an auto$o"al re!e$$i:e %e#e!t in the !y$ti! #i&ro$i$ tran$"e"&rane !on%u!tan!e re.ulator 1C'TR2 .ene on !hro"o$o"e 3. 'ro" the /e%i.ree a&o:e5 0e are a$ke% to !al!ulate the /ro&a&ility that a #uture !hil% 0ill inherit a "utant allele #ro" ea!h /arent. Sin!e the #ather i$ ho"o7y.ou$ #or the "utant CETR allele5 /1 1the /ro&a&ility that the #ather 0ill tran$"it the "utant allele2 L 1. e!au$e the "other ha$ an a##e!te% $i&lin. 0e kno0 that $he "u$t ha:e ha% t0o hetero7y.ou$ !arrier /arent$. Thu$5 the /ro&a&ility5 /G5 that the "other i$ a !arrierL GFH 1a$ i$ e:i%ent #ro" the %ia.ra" &elo0=

I# the "other i$ a !arrier5 the /ro&a&ility5 /H5 that $he 0ill tran$"it the "utant allele to the !hil% i$ 1FG. 'inally the /ro&a&ility that the !hil% 0ill inherit t0o "utant allele$5 i.e. the /ro&a&ility o# inheritin. a "utant allele #ro" the #ather an% #ro" the "other5 i$ /1 ) /G ) /H L 1FH. E%u!ational O&<e!ti:e= The /ro&a&ility that an auto$o"al re!e$$i:e %i$ea$e 0ill &e tran$"itte% to a !hil% !an &e !al!ulate% #ro" the "aternal an% /aternal /e%i.ree$.

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Q NO 6: An in#ant &orn /re"aturely to a H-9year9ol% Cau!a$ian #e"ale i$ $"all #or .e$tational a.e. Phy$i!al e)a"ination re:eal$ a &ilateral !le#t li/5 "i!ro!e/haly5 an% "i!ro/hthal"o$. Di$!era /rotru%e #ro" an u"&ili!al o/enin. in the !hil%($ a&%o"inal 0all. Whi!h o# the #ollo0in. karyoty/e$ i$ "o$t likely in thi$ !a$eK A. Tri$o"y G1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ '. >35 ?@@ Explanation: Tri$o"y 1H 1Patau $yn%ro"e2 i$ the thir% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$5 an% the "o$t $e:ere. A##e!te% !hil%ren ty/i!ally %ie 0ithin the #ir$t 0eek o# li#e5 0ith only +4 $ur:i:in. the #ir$t $i) "onth$. In the "a<ority o# tri$o"y 1H in#ant$ !yto.eneti! $tu%ie$ %e"on$trate non%i$<un!tion 1>3??5 M1H2N thi$ !hro"o$o"al a&nor"ality ari$e$ %urin. "aternal "eio$i$ I an% i$ a$$o!iate% 0ith a%:an!e% "aternal a.e. The /ro"inent /henoty/i! #eature$ o# tri$o"y 1H are a$$o!iate% 0ith an early %e#e!t in /re!hor%al "e$o%er" %e:elo/"ent. A$ a re$ult5 the "i%#a!e5 eye5 an% #ore&rain are "o$t "arke%ly a##e!te%. The !lini!al "ani#e$tation$ o# Patau $yn%ro"e in!lu%e the a&nor"alitie$ !ate.ori7e% &y $y$te" &elo0. 1. ;ea% an% ne!k= $e:ere !le#t li/ an%For /alate "i!ro/hthal"ia or ano/hthal"ia5 !olo&o"a5 !y!lo/$5 "al#or"e% or a&$ent no$e5 %ea#ne$$5 $!al/ %e#e!t$ 1a/la$ia !uti$2 G. CNS= $e:ere "ental retar%ation "i!ro!e/haly5 holo/ro$en!e/haly 1#ailure o# &rain to %i:i%e into he"i$/here$2 a&$ent ol#a!tory ner:e or &ul&5 neural tu&e %e#e!t$ H. E)tre"itie$= /oly%a!tyly5 ro!ker9&otto" #eet >. Car%ia!= PDAI atrial $e/tal %e#e!t5 :entri!ular $e/tal %e#e!t +. Renal= /oly!y$ti! ki%ney %i$ea$e E. Ga$trointe$tinal= a&%o"inal 0all %e#e!t$ a$$o!iate% 0ith o"/halo!ele or u"&ili!al hernia5 /ylori! $teno$i$ 1Choi!e A2The #etu$ 0ith Do0n $yn%ro"e 1tri$o"y G12 0ill ty/i!ally ha:e a #lat #a!e5 a&nor"al ear$5 $lante% /al/e&ral #i$$ure$5 re%un%ant $kin at na/e o# ne!k5 hy/otonia5 /el:i! %y$/la$ia5 an% $in.le tran$:er$e /al"ar !rea$e. Duo%enal atre$ia an% tra!heoe$o/ha.eal #i$tula are t0o o# the "ore #re6uently o&$er:e% .a$trointe$tinal !on%ition$. 1Choi!e 2 Clini!al "ani#e$tation$ o# tri$o"y 1- 1E%0ar%$ $yn%ro"e2 in!lu%e /ro"inent o!!i/ut "i!ro.nathia5 $"all "outh lo09$et an% "al#or"e% ear$5 an% ro!ker9&otto" #eet. Clen!he% han%$ 0ith the in%e) #in.er o:erri%in. the "i%%le #in.er an% the #i#th #in.er o:erri%in. the #ourth #in.er are !hara!teri$ti! #or thi$ !on%ition. Me!kel($ %i:erti!ulu" an% "alrotation are !o""on .a$trointe$tinal a&nor"alitie$. 1Choi!e D2 The >35 ??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% 0o"en "ay ha:e $li.htly %e!rea$e% IC $!ore$. 'e"ale ne0&orn$ 0ith thi$ karyoty/e are /heno ty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". 1Choi!e E2 The >35 ??@ 1Aline#elter $yn%ro"e2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intelli.en!e. The ty/i!al /atient i$ a tall "ale a%ult 0ith .yne!o"a$tia5 $"all te$te$5 an% in#ertility.

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1Choi!e '2The >35 ?@@ karyoty/e i$ !hara!teri7e% &y tall $tature5 $e:ere a!ne5 an% "il% %elay$ in &oth "otor an% lan.ua.e %e:elo/"ent. Male ne0&orn$ 0ith thi$ karyoty/e are /heno ty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". E%u!ational O&<e!ti:e= Tri$o"y 1H 1Patau $yn%ro"e2 "o$t o#ten o!!ur$ $e!on%ary to non%i$<un!tion %urin. "aternal "eio$i$ I. A $e:ere !on%ition tri$o"y 1H i$ $tron.ly a$$o!iate% 0ith !le#t li/ an% /alate5 /oly%a!tyly5 ro!ker9&otto" #eet an% holo/ro$en!e/haly.

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Q NO 7: A #e"ale in#ant &orn to a G-9year9ol% 0o"an #ollo0in. an un!o"/li!ate% :a.inal %eli:ery i$ #oun% to ha:e $0ellin. o# the han%$ an% a /o$terior ne!k "a$$. The "a$$ i$ !o"/o$e% o# !y$ti! $/a!e$ $e/arate% &y !onne!ti:e ti$$ue ri!h in ly"/hoi% a..re.ate$. The in#ant "o$t likely $u##er$ #ro"= A. Cri %u !hat 1+/92 $yn%ro"e . Do0n($ $yn%ro"e C. Turner($ $yn%ro"e D. A%reno.enital $yn%ro"e E. Te$ti!ular #e"ini7ation $yn%ro"e Explanation: The ne!k "a$$ %e$!ri&e% in the 6ue$tion i$ likely a !y$ti! hy.ro"a. Cy$ti! hy.ro"a$ are tu"or$ "o$t !o""only lo!ate% on the ne!k 1e$/e!ially in the /o$terior trian.le2 that are a//arent at &irth. Cy$ti! hy.ro"a$ are o#ten $een in in#ant$ 0ith Turner($ $yn%ro"e. S0ellin. o# the han%$ an% #eet 1ly"/he%e"a2 i$ another !o""on early "ani#e$tation o# thi$ !on%ition. oth !y$ti! hy.ro"a$ an% ly"/he%e"a o!!ur %ue to a&nor"alitie$ o# ly"/hati! out#lo0 in Turner($ $yn%ro"e. The $0ellin. %e!rea$e$ 0ith a.e. Ol%er !hil%ren an% a%ult$ 0ith Turner($ $yn%ro"e ha:e a !hara!teri$ti! a//earan!e that in!lu%e$= 0e&&e% ne!k5 lo0 hairline5 an% $hiel% !he$t5 $hort #ourth "eta!ar/al an% $hort $tature. Pri"ary a"enorrhea i$ the re$ult o# o:arian un%er%e:elo/"ent 1$treak o:arie$2. Patient$ #ail to %e:elo/ $e!on%ary $e) !hara!teri$ti!$. Aorti! !oar!tation i$ a !ar%io:a$!ular %e#e!t !o""only #oun% in Turner($ $yn%ro"e. 1Choi!e A2 Patient$ 0ith !ri %u !hat 1+/92 $yn%ro"e ty/i!ally ha:e a roun% #a!e5 !at9 like !ry5 an% "i!ro!e/haly. 1Choi!e 2 Neonate$ 0ith Do0n($ $yn%ro"e ha:e a !hara!teri$ti! a//earan!e a$ 0ell in!lu%in. a #lat #a!e5 o&li6ue /al/e&ral #i$$ure$5 an% e/i!anthal #ol%$. Do0n($ $yn%ro"e i$ not a$$o!iate% 0ith ly"/he%e"a or !y$ti! hy.ro"a$. 1Choi!e D2 In a%reno.enital $yn%ro"e 1!on.enital a%renal hy/er/la$ia25 /atient$ ha:e a&nor"al $e)ual %i##erentiation %ue to %e#e!ti:e hor"one $ynthe$i$ in the a%renal .lan%$. The "o$t !o""on a%reno.enital $yn%ro"e i$ G19 hy%ro)yla$e %e#i!ien!y. Patient$ /re$ent at &irth 0ith a"&i.uou$ .enitalia 1#e"ale$ only2 an% $y"/to"$ o# $alt 0a$tin.. 1Choi!e E2 Te$ti!ular #e"ini7ation $yn%ro"e 1al$o !alle% an%ro.en in$en$iti:ity $yn%ro"e2 o!!ur$ %ue to a %e#e!t in te$to$terone re!e/tor$. Neonate$ 0ith karyoty/e >E ?@ a//ear to &e /heno ty/i!ally nor"al #e"ale$. There i$ a &lin%9 en%e% :a.inal /ou!h 0ithout a uteru$. E%u!ational O&<e!ti:e= Turner($ $yn%ro"e 1>+ ?O2 "ani#e$t$ in the neonate 0ith ly"/he%e"a an% !y$ti! hy.ro"a$. Short $tature5 /ri"ary a"enorrhea an% !oar!tation o# the aorta are the other i"/ortant !lini!al #eature$ o# Turner($ $yn%ro"e in a%ult$.

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Q NO 8: A >G9year9ol% Cau!a$ian "ale 0ho 0a$ /re:iou$ly %ia.no$e% 0ith %e/re$$ion i$ no0 e)/erien!in. in:oluntary .ri"a!in. an% $tran.e "o:e"ent$ o# hi$ ar"$ an% le.$. Neurolo.i!al e)a"ination $ho0$ nor"al $tren.th an% nor"al %ee/ ten%on re#le)e$. No $en$ory %e#i!it$ are note%. The /atient($ .ran%#ather %ie% o# a neurolo.i!al %i$ea$e at E+ year$ ol%5 an% the /atient($ #ather %ie% o# a $i"ilar %i$ea$e at +-. That thi$ /atient ha$ an earlier on $et o# %i$ea$e than either hi$ #ather or .ran%#ather i$ "o$t likely e)/laine% &y 0hi!h o# the #ollo0in.K In!rea$e% /enetran!e . Pleiotro/y C. Anti!i/ation D. Mo$ai!i$" E. Partial %eletion '. Geno"i! i"/rintin.

A.

Explanation: ;untin.ton %i$ea$e "ani#e$t$ 0ith the tria% o# "o:e"ent %i$or%er 1!horea25 &eha:ioral a&nor"alitie$ 1a..re$$i:ene$$5 a/athy or %e/re$$ion25 an% %e"entia. ;untin.ton %i$ea$e i$ tran$"itte% a$ an auto$o"al %o"inant trait 0ith 1,,4 /enetran!e5 "eanin. that i# a !hil% inherit$ the a&nor"al .ene5 that !hil% 0ill ine:ita&ly %e:elo/ ;untin.ton %i$ea$e. Mo$t /atient$ %e:elo/ $y"/to"$ in their>o$ or+o$. An earlier a.e o# on$et i$ a$$o!iate% 0ith a lar.er nu"&er o# trinu!leoti%e re/eat$. Durin. $/er"ato.ene$i$5 CAG re/eat$ in the a&nor"al ;D .ene ra/i%ly in!rea$e. Thu$5 /atient$ 0ho re!ei:e an a&nor"al .ene #ro" their #ather$ ten% to %e:elo/ the %i$ea$e earlier in li#e. 1The nu"&er o# trinu!leoti%e re/eat$ on ;D .ene re"ain$ the $a"e %urin. "aternal tran$"i$$ion.2 The ten%en!y #or !lini!al $y"/to"$ to 0or$en an%For o!!ur earlier in $u&$e6uent .eneration$ i$ !alle% anti!i/ation. Anti!i/ation i$ !o""on in %i$or%er$ a$$o!iate% 0ith trinu!leoti%e re/eat$5 a$ in 'ra.ile ? $yn%ro"e5 "yotoni! %y$tro/hy5 an% 'rie%rei!h ata)ia. 1Choi!e A2 The tran$"i$$ion o# an a&nor"al .ene #ro" a /arent to a !hil% %oe$ not al0ay$ !au$e %i$ea$e. 'or e)a"/le 0o"en 0ith RCA9G "utation$ %o not al0ay$ %e:elo/ &rea$t !an!er. The likelihoo% that the /ro/ertie$ o# a .ene 0ill &e e)/re$$e% i$ !alle% /enetran!e. ;untin.ton %i$ea$e i$ a %i$or%er 0ith 1,,4 /enetran!eN all in%i:i%ual$ 0ho ha:e an a&nor"al ;D .ene 0ill %e:elo/ ;untin.ton %i$ea$e. 1Choi!e 2 So"eti"e$5 one .ene "utation lea%$ to "ulti/le /henoty/i! a&nor"alitie$5 a .eneti! /heno"enon na"e% B/leiotro/y.C In ;untin.ton %i$ea$e5 /leiotro/y i$ !learly at 0ork &e!au$e the "utation o# one .ene 1;D2 !au$e$ %y$#un!tion o# &eha:ior5 o# "o:e"ent5 an% o# !o.nition. 1Choi!e D2The /re$en!e o# t0o /o/ulation$ o# !ell$ 0ith %i##erent .enoty/e$ in one /atient i$ !alle% "o$ai!i$". E)a"/le$ o# "o$ai!i$" in!lu%e "il%er #or"$ o# Turner 1.enoty/e >E??F>+?,25 Aline#elter 1>E?@F>3??@25 an% Do0n $yn%ro"e$. 1Choi!e E2 Deletion i$ the lo$$ o# .eneti! "aterial. E)a"/le$ o# %eletion are DiGeor.e $yn%ro"e 1GG6 11 "i!ro %eletion$2 an% !ri9%u9!hat $yn%ro"e 1+/ %eletion2. 1Choi!e '2 Geno"i! i"/rintin. i$ a $ele!ti:e ina!ti:ation o# the .ene$ o# either "aternal or /aternal ori.in5 !au$in. a /heno"enon $o"eti"e$ !alle% B/arent9o#9 ori.in .ene e)/re$$ion.C Geno"i! i"/rintin. o!!ur$ in Pra%er9Willi an% An.el"an $yn%ro"e$. oth !on%ition$ in:ol:e %eletion o# the $a"e .ene on the $a"e !hro"o$o"e 11+25 &ut ye0 %i##erent !lini!al "ani#e$tation$ o!!ur %e/en%in. on the ori.in o# the "utation. I# the %eletion !o"e$ #ro" the #ather5 Pra%er9Willi $yn%ro"e o!!ur$Oa##e!te% !hil%ren $ho0 in$atia&le hun.er an% thir$t an% e"otional la&ilityN

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0herea$5 %eletion$ inherite% #ro" the "other re$ult in An.el"an $yn%ro"eOal$o !alle% Bha//y /u//etC $yn%ro"e &e!au$e !hil%ren e)hi&it <erk "o:e"ent$ 1like a "arionette2 an% an al"o$t9/atholo.i!ally ha//y %i$/o$ition. E%u!ational O&<e!ti:e= An in!rea$e% nu"&er o# trinu!leoti%e re/eat$ on the ;D .ene i$ a$$o!iate% 0ith ;untin.ton %i$ea$e. The lar.er the nu"&er o# the re/eat$5 the earlier the on$et o# the %i$ea$e. Trinu!leoti%e e)/an$ion o!!ur$ %urin. /aternal tran$"i$$ion5 !au$in. a .eneti! /heno"enon !alle% anti!i/ation.

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Q NO 9: A HG9year9ol% "ale /re$ent$ to the ER 0ith re!ent on$et o# $e:ere #ati.ue5 e)ertional %y$/nea an% #e:er. Cyto.eneti! $tu%ie$ o# thi$ /atient($ &loo% !ell$ %e"on$trate a 1+N 13 !hro"o$o"al tran$lo!ation. Whi!h o# the #ollo0in. /rotein$ i$ "o$t likely "al#un!tionin. in the a##e!te% !ell$K A. E/i%er"al .ro0th #a!tor re!e/tor . Platelet %eri:e% .ro0th #a!tor re!e/tor C. Retinoi! a!i% re!e/tor D. GTP9&in%in. /rotein E. Retino&la$to"a .ene /ro%u!t Explanation: A!ute "yelo.enou$ leuke"ia 1AML2 i$ !hara!teri7e% &y #ailure o# i""ature "yeloi% /re!ur$or$ 1"yelo&la$t$2 to %i##erentiate into "ature .ranulo!yte$. It i$ %i:i%e% into ei.ht ty/e$5 M, throu.h M3. The MH :ariant o# AMLI a!ute /ro"yelo!yti! leuke"ia5 i$ a$$o!iate% 0ith the !yto.eneti! a&nor"ality t11+N132. ;ere the .ene #or retinoi! a!i% re!e/tor al/ha #ro" !hro"o$o"e 13 i$ tran$#erre% to !hro"o$o"e 1+ in a lo!ation a%<a!ent to the PML 1/ro"yelo!yti! leuke"ia2 .ene. 'u$ion o# the$e t0o .ene$ /ro%u!e$ a !hi"eri! .ene /ro%u!t PMLFRARa5 0hi!h !o%e$ #or an a&nor"al retinoi! a!i% re!e/tor. Thi$ a&nor"al #u$ion .ene /ro%u!t inhi&it$ "yelo&la$t %i##erentiation5 /ro%u!in. a!ute /ro"yelo!yti! leuke"ia. The !lini!al "ani#e$tation$ o# AML5 in!lu%in. ane"ia 1#ati.ue5 /allor25 thro"&o!yto/enia 1/ete!hiae5 he"orrha.e$2 an% neutro/enia 1#e:er o//ortuni$ti! in#e!tion$2 re$ult #ro" "arro0 re/la!e"ent &y leuke"i! !ell$. 1Choi!e A2 Mutation$ o# the .ene$ that !o%e #or the e/i%er"al .ro0th #a!tor re!e/tor$ are a$$o!iate% 0ith non9$"all !ell lun. !ar!ino"a 1er& 125 &rea$t !an!er 1er& G aka ;ERGFneu25 an% $o"e o:arian an% .a$tri! tu"or$. 1Choi!e 2 De#e!ti:e /latelet %eri:e% .ro0th #a!tor re!e/tor /lay$ a role in the /atho.ene$i$ o# !hroni! "yelo"ono!yti! leuke"ia. 1Choi!e D2 GTP9&in%in. /rotein$ are in:ol:e% in !ellular $i.nal tran$%u!tion. 1Choi!e E2 An a&nor"al R& .ene /re%i$/o$e$ to %e:elo/"ent o# retino&la$to"a an% o$teo$ar!o"a. E%u!ational O&<e!ti:e= The !yto.eneti! %e#e!t t11+N132 i$ a$$o!iate% 0ith a!ute /ro"yelo!yti! leuke"ia 1AML ty/e MH2. Tran$lo!ation o# the .ene #or the retinoi! a!i% re!e/tor al/ha #ro" !hro"o$o"e 13 to !hro"o$o"e 1+ lea%$ to #or"ation o# the #u$ion .ene PMLFRARP. Thi$ a&nor"al #u$ion .ene /ro%u!t inhi&it$ %i##erentiation o# "yelo&la$t$ an% tri..er$ the %e:elo/"ent o# a!ute /ro"yelo!yti! leuke"ia.

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Q NO 10: A G+9year9ol% "ale i$ &ein. e:aluate% #or in#ertility. On /hy$i!al e)a"ination5 he ha$ &ilateral .yne!o"a$tia an% $"all #ir" te$te$. ;i$ e)tre"itie$ are a&nor"ally lon.. 'urther e:aluation 0ill "o$t likely $ho0 0hi!h o# the #ollo0in.K Seru" L; Seru" 'S; Seru" te$to$terone S/er" !ount A. De!rea$e% De!rea$e% De!rea$e% De!rea$e% . Nor"al Nor"al Nor"al None C. De!rea$e% Nor"al In!rea$e% De!rea$e% D. In!rea$e% In!rea$e% De!rea$e% De!rea$e% E. Nor"al De!rea$e% Nor"al De!rea$e% Explanation: The /atient %e$!ri&e% in thi$ :i.nette ha$ hy/o.ona%i$"5 $"all #ir" te$te$5 elon.ate% li"&$5 an% .yne!o"a$tia5 'in%in.$ hi.hly $u..e$ti:e o# Aline#elter $yn%ro"e. In Aline#elter $yn%ro"e5 the $e"ini#erou$ tu&ule$ are /ro.re$$i:ely %e$troye% an% hyalini7e%5 !au$in. the te$te$ to &e $"all an% #ir". Seru" inhi&in le:el$ are %e!rea$e% a$ a re$ult o# the %a"a.e to the $e"ini#erou$ tu&ule$. The inter$titial Ley%i. !ell$ are %a"a.e% a$ 0ell5 re$ultin. in lo0 te$to$terone le:el$ an% ere!tile %y$#un!tion. e!au$e o# the lo0 !ir!ulatin. le:el$ o# te$to$terone an% inhi&in5 L; an% ES; are ele:ate% 1lo$$ o# #ee%&a!k inhi&ition2. The hy/o.ona%i$" !au$e$ e/i/hy$eal #u$ion to &e %elaye%5 hen!e the elon.ate% li"&$. Mo$t /atient$ 0ith Aline#elter $yn%ro"e are in#ertile. The ty/i!al .enoty/e in /atient$ 0ith Aline#elter $yn%ro"e i$ >3 ??@5 0ith "o$t o# the !lini!al "ani#e$tation$ re$ultin. #ro" the e)tra ? !hro"o$o"e. Thi$ .enoty/e !an o!!ur 0hen there i$ Bnon9%i$<un!tionC o# the $e) !hro"o$o"e$ %urin. "eioti! %i:i$ion in either /arent. 1Choi!e A2 Lo0 L; an% ES; alon. 0ith lo0 te$to$terone are !on$i$tent 0ith !entral hy/o.ona%i$"5 0hi!h !an re$ult #ro" %a"a.e to the hy/othala"u$ or /ituitary .lan%. The !on.enital a&$en!e o# GnR;9$e!retin. neuron$ i$ !alle% Aall"ann($ $yn%ro"e. 1Choi!e 2 A /atient 0ith a nor"al hor"onal /ro#ile &ut la!kin. $/er" "ay ha:e an o&$tru!tion $o"e0here alon. the /ath #ro" the te$te$ to the $e"inal #lui%. 1Choi!e C2 ;ere L; i$ $u//re$$e%5 'S; i$ nor"al5 an% te$to$terone i$ ele:ate%5 in the $ettin. o# a lo0 $/er" !ount. Thi$ !o"&ination i$ ty/i!al o# treat"ent 0ith an%ro.en$ or ana&oli! $teroi%$ 0ith an%ro.eni! /ro/ertie$. ;i.h an%ro.en le:el$ $u//re$$ L; $e!retion5 thu$ %e!rea$in. en%o.enou$ te$to$terone /ro%u!tion. De$/ite the hi.h !ir!ulatin. le:el$ o# an%ro.en5 the$e /atient$ ha:e a lo0 $/er" !ount. Thi$ i$ &e!au$e hi.h lo!al an%ro.en !on!entration$ are ne!e$$ary #or $/er"ato.ene$i$5 &ut here5 the lo!al $e"ini#erou$ tu&ule !on!entration o# te$to$terone i$ $u&o/ti"al. O:erti"e there i$ $o"e atro/hy o# the $e"ini#erou$ tu&ule$ !au$in. a %e!rea$e in te$ti!ular $i7e. 1Choi!e E2 In thi$ !hoi!e L; i$ nor"al5 'S; i$ ele:ate%5 an% te$to$terone i$ nor"al5 0ith a lo0 $/er" !ount. Thi$ i$ ty/i!al o# /atient 0ith !ry/tor!hi%i$" 1or another !on%ition that %a"a.e$ the $e"ini#erou$ tu&ule$5 $u!h a$ or!hiti$2. In the$e !on%ition$5 the $e"ini#erou$ tu&ule$ are %a"a.e% an% the inter$titial Ley%i. !ell$ are /re$er:e%. Se"ini#erou$ tu&ule %a"a.e lea%$ to ele:ate% 'S; le:el$ 1$e!on%ary to lo0 inhi&in le:el$2. L; an% te$to$terone le:el$ are nor"al &e!au$e the te$to$terone9 /ro%u!in. Ley%i. !ell$ are not a##e!te%. E%u!ational O&<e!ti:e= Aline#elter $yn%ro"e i$ !hara!teri7e% &y hy/o.ona%i$"5 eunu!hoi% ha&itu$5 $"all #ir" te$te$5 an% .enoty/e >3 ??@.

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Q NO 11: A $tu%y !on%u!te% on tran$.eni! "ou$e "o%el$ o# ;untin.ton %i$ea$e atte"/te% to re:eal the "ole!ular /atho.ene$i$ o# thi$ %i$or%er. It 0a$ #oun% that the a&nor"al huntin.tin /rotein !o%e% #or &y the ;D .ene %e!rea$e$ e)/re$$ion o# a nu"&er o# other .ene$. A$ a re$ult5 $o"e neurotro/hi! /rotein$ are not $ynthe$i7e%. Inhi&ition o# .ene e)/re$$ion in ;untin.ton %i$ea$e o!!ur$ :ia= A. DNA a!etylation . ;y/er "ethylation o# hi$tone$ C. Thy"i%ine %i"eri7ation D. Mutation o# ho"eo%o"ain .ene E. Su//re$$ion o# "RNA $ynthe$i$ Explanation: ;untin.ton %i$ea$e i$ an auto$o"al9%o"inant neuro%e.enerati:e %i$ea$e 0ith !o"/lete /enetran!e that ha$ &een lo!ali7e% to a re.ion on the #ourth !hro"o$o"e. It %e:elo/$ %ue to an in!rea$e in the nu"&er o# CAG trinu!leoti%e re/eat$ on the ;D .ene that !o%e$ #or the a&nor"al /rotein huntin.tin. Thi$ a&nor"al .ene /ro%u!t #un!tion$ to %e!rea$e the e)/re$$ion o# other .ene$ &y inhi&itin. their tran$!ri/tion. Thi$ i$ !alle% tran$!ri/tional re/re$$ion or $ilen!in.5 an% /lay$ an i"/ortant role in /atho.ene$i$ o# ;untin.ton %i$ea$e. Althou.h all !ell$ in the hu"an &o%y ha:e the $a"e .eno"e5 they %e:elo/ into %i##erent :ariant$ $/e!i#i! #or e:ery or.an an% ti$$ue. Su!h %i##erentiation i$ /o$$i&le %ue to e)/re$$ion o# $o"e .ene$ an% B$ilen!in.C o# other$. Thi$ re.ulation o# tran$!ri/tion o!!ur$ in /art %ue the /re$en!e o# hi$tone$5 $"all /rotein$ that !o"/le) 0ith DNA to "ake !ertain re.ion$ o# the .eno"e not a!!e$$i&le #or tran$!ri/tion. Methylation o# a"ino a!i% re$i%ue$ in hi$tone$ in!rea$e$ their a&ility to re/re$$ tran$!ri/tion5 an% in ;untin.ton %i$ea$e $o"e hi$tone #ra."ent$ are hy/er "ethylate% lea%in. to in!rea$e% $ilen!in. o# !ertain .ene$. Re!ent re$ear!h on "ou$e "o%el$ ha$ $ho0n that the anti"eta&olite "ithra"y!in %e!rea$e$ "ethylation o# hi$tone$ an% "ay /ro:e u$e#ul in the treat"ent o# ;untin.ton %i$ea$e. 1Choi!e A2 A!etylation o# hi$tone$ an% DNA 0eaken$ the DNA9hi $tone &on% an% "ake DNA #ra."ent$ a!!e$$i&le #or tran$!ri/tion #a!tor$ an% RNA /oly"era$e$. A!etylation5 there#ore5 enhan!e$ .ene tran$!ri/tion 0hile "ethylation %e!rea$e$ tran$!ri/tion. 1Choi!e C2 Thy"i%ine %i"eri7ation i$ one o# the "e!hani$"$ o# DNA %a"a.e in%u!e% &y UD ra%iation. 1Choi!e$ D an% E2 Mutation o# ho"eo%o"ain 1ho"eo&o)2 .ene$ 0oul% theoreti!ally !au$e alteration$ in the &o%y $tru!ture o# an ani"al or lea% to $/ontaneou$ a&ortion &y lea%in. to a &o%y $tru!ture in!o"/ati&le 0ith li#e. Su//re$$ion o# "RNA $ynthe$i$ 0oul% lea% to #ailure o# /rotein $ynthe$i$ an% ha$ not &een #oun% to /lay any role in ;untin.ton %i$ea$e. E%u!ational O&<e!ti:e= Alteration o# .ene e)/re$$ion in ;untin.ton %i$ea$e i$ &elie:e% to o!!ur %ue to hy/er "ethylation o# hi$tone$. ;y/er "ethylate% hi$tone$ &in% DNA an% /re:ent it$ tran$!ri/tion lea%in. to %i$ru/tion o# $ynthe$i$ o# $o"e neurotro/hi! /rotein$.

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Q NO 12: An in#ant &orn /re"aturely to a >G9year9ol% Cau!a$ian #e"ale i$ $"all #or .e$tational a.e. Phy$i!al e)a"ination re:eal$ "i!ro!e/haly5 lo09$et ear$5 /ro"inent o!!i/ut an% $"all "an%i&le. The in#ant($ #i$t$ are !len!he% an% the #in.er$ o:erla/. A &ilateral #oot %e#or"ity i$ o&$er:e%. Whi!h o# the #ollo0in. i$ the "o$t likely karyoty/e a&nor"ality in thi$ in#antK A. Tri$o"y G1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ Explanation: Tri$o"y 1- 1E%0ar%$ $yn%ro"e2 i$ the $e!on% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$5 0ith tri$o"y G1 the "o$t !o""on. Ninety /er!ent o# E%0ar%$($ $yn%ro"e !a$e$ re$ult #ro" non%i$<un!tion5 0ith !yto.eneti! $tu%ie$ %e"on$tratin. a #ull tri$o"y 1>35 M 1-2. The !lini!al "ani#e$tation$ o# E%0ar%$($ $yn%ro"e in!lu%e the a&nor"alitie$ !ate.ori7e% &y $y$te" &elo0. 1. 'a!e= "i!ro.nathia5 "i!ro$to"ia5 eye %e#e!t$ 1"i!ro/hthal"ia5 !atara!t$ !olo&o"a25 lo09$et an% "al#or"e% ear$5 /ro"inent o!!i/ut G. CNS= "i!ro!e/haly5 neural tu&e %e#e!t$ 1e.5 "enin.o!ele5 anen!e/haly25 holo/ro$en!e/haly5 Arnol%9Chiari "al#or"ation5 $e:ere "ental retar%ation5 %elaye% /$y!ho"otor %e:elo/"ent H. Mu$!ulo$keletal= !len!he% han%$ 0ith o:erla//in. #in.er$ 1in%e) #in.er o:erri%e$ the "i%%le #in.er an% #i#th #in.er o:erri%e$ the #ourth #in.er25 ro!ker9&otto" #eet5 $hort $ternu"5 an% hy/ertonia >. Car%ia!= :entri!ular $e/tal %e#e!t5 /atent %u!t arterio$u$ +. Ga$trointe$tinal= Me!kel($ %i:erti!ulu"5 "alrotation Tri$o"y 1- !an &e %ete!te% /renatally 0ith the u$e o# ultra$oun%. Su..e$ti:e #in%in.$ in!lu%e intrauterine .ro0th re$tri!tion an% /olyhy%ra"nio$5 e$/e!ially in a #etu$ 0ith a&nor"al han% arran.e"ent. 1Choi!e A2 The #etu$ 0ith Do0n $yn%ro"e 1tri$o"y G12 0ill ty/i!ally ha:e a #lat #a!e5 a&nor"al ear$5 $lante% /al/e&ral #i$$ure$5 re%un%ant $kin at na/e o# ne!k5 hy/otonia5 /el:i! %y$/la$ia5 an% $in.le tran$:er$e /al"ar !rea$e. 1Choi!e C2 Unlike neonate$ 0ith E%0ar%$ $yn%ro"e5 neonate$ 0ith tri$o"y 1H 1Patau $yn%ro"e2 ha:e !le#t li/ an% /alate5 /oly%a!tyly an% o"/halo!ele. Patau $yn%ro"e i$ not a$$o!iate% 0ith lo09$et ear$ an% o:erla//in. #in.er$. 1Choi!e D2 The >35 ??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% 0o"en "ay ha:e $li.htly %e!rea$e% IQ $!ore$. 'e"ale ne0&orn$ 0ith thi$ karyoty/e are /henoty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". 1Choi!e E2 The >35 ??@ 1Aline#elter $yn%ro"e2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intelli.en!e. The ty/i!al /atient i$ a tall "ale a%ult 0ith .yne!o"a$tia5 $"all te$te$5 an% in#ertility. Male ne0&orn$ 0ith thi$ karyoty/e are /henoty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". The !lini!al #in%in.$ %o not &e!o"e a//arent until a%ole$!en!e or a%ulthoo%. E%u!ational O&<e!ti:e= Neonate$ 0ith E%0ar%$($ $yn%ro"e 1>35 ??5 M1-2 ha:e $"all <a0$ 1"i!ro.nathia25 $"all eye$ 1"i!ro/hthal"ia25 an% "al#or"e% an% lo09$et ear$. Note that ro!ker9 &otto" #eet are $een5 a$ 0ith Patau $yn%ro"e 1tri$o"y 1H2. The /re$en!e o# !len!he% han%$ 0ith o:erla//in. #in.er$ i$ !on$i%ere% one o# the %i$tin.ui$hin. #eature$ o# thi$ $yn%ro"e.

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Q NO 13: A neonate &orn to >19year9ol% 0o"an in her HJth 0eek o# .e$tation ha$ a #lattene% #a!e an% e/i!anthal #ol%$. The !hil%($ e!ho!ar%io.ra/hy re:eal$ an en%o!ar%ial !u$hion %e#e!t. Whi!h o# the #ollo0in. "o$t likely o!!urre% /rior to !on!e/tionK A. Meioti! non9%i$<un!tion . Ro&ert$onian tran$lo!ation C. E)/an$ion o# trinu!leoti%e re/eat$ D. 'or"ation o# #ra.ile $ite E. Ina!ti:ation o# one !hro"o$o"e '. Deletion o# !hro"o$o"al /art Explanation: The in#ant %e$!ri&e% in thi$ !lini!al :i.nette ha$ $o"e ty/i!al #eature$ o# Do0n $yn%ro"e. Chara!teri$ti! a//earan!e o# the$e /atient$ in!lu%e$ #lat #a!ie$5 e/i!anthal #ol%$5 o&li6ue /al/e&ral #i$$ure$ an% a $in.le /al"ar !rea$e. Con.enital heart %e#e!t$ are $een in +,4 o# /atient$ 0ith Do0n $yn%ro"e5 an% en%o!ar%ial !u$hion %e#e!t$ are "o$t !o""only o&$er:e%. The "a<ority o# /atient$ 0ith Do0n $yn%ro"e ha:e tri$o"y G1 that o!!ur$ a$ a re$ult o# !hro"o$o"al non%i$<un!tion 1#ailure o# !hro"o$o"e$ to $e/arate2 %urin. the #ir$t "eioti! %i:i$ion o# the o:u". The in!i%en!e o# thi$ a&nor"ality in!rea$e$ 0ith "aternal a.e. 1Choi!e 2 Ro&ert$onian tran$lo!ation o!!ur$ %ue to a &reak near the !entro"ere$ o# t0o !hro"o$o"e$5 0ith tran$#er o# .eneti! "aterial &et0een the !hro"o$o"e$. Ro&ert$onian tran$lo!ation a!!ount$ #or H9>4 o# Do0n $yn%ro"e !a$e$5 an% i$ inherite% #ro" one o# the /arent$5 "o$t !o""only the "other5 %urin. !on!e/tion. Co""on tran$lo!ation$ are t11>=G12 an% t1G1 GG2. 1Choi!e C2 Di$or%er$ a$$o!iate% 0ith e)/an$ion o# trinu!leoti%e re/eat$ on the $/e!i#i! .ene in!lu%e ;untin.ton %i$ea$e5 "yotoni! %y$tro/hy an% #ra.ile ? $yn%ro"e. 1Choi!e D2 'or"ation o# a #ra.ile $ite on ? !hro"o$o"e i$ !hara!teri$ti! #or #ra.ile ? $yn%ro"e. 1Choi!e E2 Sele!ti:e ina!ti:ation o# "aternal or /aternal allele$ i$ !alle% i"/rintin.. A$ a re$ult o# thi$ /ro!e$$5 the $a"e .eneti! a&nor"ality !an !au$e %i##erent %i$or%er$ 0hen inherite% #ro" the "other or the #ather. Pra%er9Willi an% An.el"an $yn%ro"e$ are the !la$$i! e)a"/le$ o# $u!h %i$or%er$. 1Choi!e '2 Many inherite% %i$ea$e$ are !au$e% &y lo$$ o# /art o# !hro"o$o"e 1%eletion2. Cri9%u9!hat $yn%ro"e 1+/ %eletion25 DiGeor.e $yn%ro"e 1GG611 "i!ro%eletion2 an% Pra%er9Willi $yn%ro"e 1l+6 %eletion2 are $o"e e)a"/le$. E%u!ational O&<e!ti:e= Do0n $yn%ro"e i$ a$$o!iate% 0ith !hara!teri$ti! /hy$i!al e)a" #in%in.$ $u!h a$ a #lattene% #a!ie$5 e/i!anthal #ol%$5 o&li6ue /al/e&ral #i$$ure$5 $in.le /al"ar !rea$e5 $hortene% #i#th %i.it5 lar.e ton.ue an% other$. Con.enital heart %e#e!t$5 e$/e!ially en%o!ar%ial !u$hion %e#e!t$5 are !o""on in !hil%ren 0ith Do0n($ $yn%ro"e. The "a<ority o# !a$e$ o!!ur %ue to "aternal "eioti! non%i$<un!tion.

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Q NO 14: A E,9year9ol% "ale 0ith /ainle$$ he"aturia i$ #oun% to ha:e a ri.ht9$i%e% renal "a$$. There i$ no $i.ni#i!ant #a"ily hi$tory. Cytolo.i! e:aluation o# the "a$$ $ho0$ "ali.nant !ell$ 0ith !hro"o$o"e S/ %eletion. The %eletion "o$t likely in:ol:e$ 0hi!h o# the #ollo0in. .ene$K A. R . D;L C. NE91 D. WT91 E. RCA91 Explanation: Gi:en the /re$entation o# he"aturia /lu$ renal "a$$5 the /atient "o$t likely ha$ renal !ell !ar!ino"a. The "a<ority o# renal !ell neo/la$"$ are $/ora%i!. A $"all nu"&er o# !a$e$ are here%itary5 $u!h a$ tho$e a$$o!iate% 0ith Don ;i//el9Lin%au %i$ea$e. Don ;i//el9 Lin%au %i$ea$e i$ an auto$o"al %o"inant %i$or%er !hara!teri7e% &y !ere&ellar he"an.io&la$to"a$5 !lear !ell renal !ar!ino"a$ an% /heo!hro"o!yto"a$. Renal !ell !ar!ino"a %e:elo/$ in nearly >,4 o# the$e /atient$5 an% i$ a "a<or !au$e o# %eath. All /atient$ 0ith Don ;i//el9Lin%au %i$ea$e ha:e a %eletion o# the D;L .ene on !hro"o$o"e H/. Althou.h Don ;i//el9Lin%au %i$ea$e i$ rare5 %eletion$ or "utation$ o# the D;L .ene are relati:ely !o""on. In #a!t %e#e!t$ o# the D;L .ene are #oun% in the "a<ority o# /atient$ 1>,9+,42 0ith $/ora%i! renal !ell !ar!ino"a. The D;L .ene i$ a tu"or $u//re$$or .ene. Renal !ell !ar!ino"a i$ the only a&nor"ality a$$o!iate% 0ith %eletion$ or "utation$ o# thi$ .ene. 1Choi!e A2 The R anti9on!o.ene i$ lo!ate% on !hro"o$o"e 1H. Mutation$ o# thi$ .ene lea% to the %e:elo/"ent o# retino&la$to"a an% o$teo$ar!o"a. 1Choi!e C2 NE9i i$ lo!ate% on !hro"o$o"e 13. Mutation$ o# thi$ .ene !au$e neuro#i&ro"ato$i$ ty/e 1. 1Choi!e D2 Mutation$ o# the WI9i anti9on!o.ene are a$$o!iate% 0ith the %e:elo/"ent o# Wil"$ tu"or. Thi$ .ene i$ lo!ate% on !hro"o$o"e 11. 1Choi!e E2 Mutation$ o# the RCA91 .ene /ut /atient$ at in!rea$e% ri$k #or &rea$t an% o:arian !an!er. E%u!ational O&<e!ti:e= Patient$ 0ith &oth $/ora%i! an% here%itary 1a$$o!iate% 0ith Don ;i//el9Lin%au %i$ea$e2 renal !ell !ar!ino"a$ are #oun% to ha:e %eletion$ o# the D;L .ene on !hro"o$o"e H/.

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Q NO 15: A Cau!a$ian ne0&orn 0ith #a!ial %y$"or/hia an% !le#t /alate i$ #oun% to ha:e a %eletion in:ol:in. the lon. ar" o# !hro"o$o"e GG. The$e #in%in.$ are "o$t !on$i$tent 0ith= A. Aarta.ener($ $yn%ro"e . Tu&erou$ $!lero$i$ C. DiGeor.e $yn%ro"e D. 'rie%rei!h($ ata)ia E. Mar#an $yn%ro"e '. Do0n $yn%ro"e G. Turner($ $yn%ro"e Explanation: Deletion$ in:ol:in. the lon. ar" o# !hro"o$o"e GG !an re$ult in #a!ial5 !ar%ia! an% i""unolo.i!al a&nor"alitie$. DiGeor.e $yn%ro"e i$ one $u!h "ani#e$tation. DiGeor.e $yn%ro"e i$ %e#ine% &y thy"i! a/la$ia an% #ailure o# /arathyroi% #or"ation5 %ue to %e#e!ti:e e"&ryoni! %e:elo/"ent o# the thir% an% #ourth /haryn.eal /ou!he$. Patient$ ty/i!ally /re$ent 0ith hy/o!al!e"i! tetany an% re!urrent :iral an% #un.al in#e!tion$ %ue to T9!ell %e#i!ien!y. Car%ia! %e#e!t$ a$$o!iate% 0ith thi$ $yn%ro"e are Tetralo.y o# 'allot an% interru/te% aorti! ar!h. Chro"o$o"e GG6 11.G %eletion$ are #oun% in J,4 o# !a$e$ o# DiGeor.e $yn%ro"e. 1Choi!e A2 Aarta.ener $yn%ro"e /ro%u!e$ i""otile !ilia %ue to an auto$o"al re!e$$i:e "i!rotu&ular %e#e!t. Male in#ertility5 re!urrent $inu$iti$5 an% &ron!hie!ta$i$ re$ult. There i$ an a$$o!iation 0ith $itu$ in:er$u$. 1Choi!e 2 Tu&erou$ $!lero$i$ i$ an auto$o"al %o"inant $yn%ro"e !hara!teri7e% &y !utaneou$ an.io#i&ro"a$ 1a%eno"a $e&a!eu"25 $ei7ure$5 an% "ental retar%ation. Patholo.i!al le$ion$ in!lu%e CNS ha"arto"a$ an% &eni.n neo/la$"$5 renal an% other :i$!eral !y$t$5 a :ariety o# other ha"arto"a$5 an% !ar%ia! rha&%o"yo"a$. 1Choi!e D2 'rie%rei!h($ ata)ia i$ an auto$o"al re!e$$i:e $/ino!ere&ellar %e.eneration 0ith /re%o"inantly $/inal ata)ia. It i$ not u$ually a$$o!iate% 0ith #a!ial or /alatal "al#or"ation$5 &ut !an &e a$$o!iate% 0ith hy/ertro/hi! !ar%io"yo/athy. 1Choi!e E2 Mar#an $yn%ro"e i$ an auto$o"al %o"inant %e#e!t in a !onne!ti:e ti$$ue .ly!o/rotein that !an !au$e !y$ti! "e%i!al ne!ro$i$ o# the aorta. It i$ not o#ten a$$o!iate% 0ith a !le#t /alate5 &ut rather a hi.h ar!he% /alate5 !ro0%e% teeth an% a narro0 #a!e. 1Choi!e '2 Do0n $yn%ro"e re$ult$ #ro" tri$o"y G1. Patient$ ha:e #lat #a!ie$5 /ro"inent e/i!anthal #ol%$5 an% o!!a$ionally a !le#t /alate. 1Choi!e G2 Turner($ $yn%ro"e i$ an ?C $e) !hro"o$o"e %i$or%er re$ultin. in $hort $tature5 0e&&e% ne!k5 o:arian #ailure5 an% /o$$i&le !oar!tation o# the aorta. E%u!ational O&<e!ti:e= A :ariety o# .eneti! %i$or%er$ !an re$ult in #a!ial an%For /alatal "al#or"ation$5 in!lu%in. %eletion$ o# the lon. ar" o# !hro"o$o"e GG. ;o0e:er %eletion$ in:ol:in. the lon. ar" o# !hro"o$o"e GG are al$o a$$o!iate% 0ith DiGeor.e $yn%ro"e 1!on.enital thy"i! an% /arathyroi% a/la$ia5 !on.enital !ar%io:a$!ular ano"alie$2.

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Q NO 16: In a $"all !ity 0ith a $ta&le Cau!a$ian /o/ulation5 the !arrier #re6uen!y #or !y$ti! #i&ro$i$ i$ 1FH, Cau!a$ian in%i:i%ual$. In a near&y !o""unity5 the !y$ti! #i&ro$i$ !arrier #re6uen!y in A$ian in%i:i%ual$ i$ 1F1,,. What i$ the /ro&a&ility that a !hil% &orn to a "other #ro" the Cau!a$ian !o""unity an% a #ather #ro" the A$ian !o""unity 0ill $u##er #ro" the %i$ea$eK A. 1FJ,, . 1F1,,, C. 1FH,,, D. 1FE,,, E. 1F1G,,, Explanation: The "other in thi$ $!enario ha$ a 1FH, /ro&a&ility o# !arryin. the "utant C'TR allele an% the #ather ha$ a 1F1,, /ro&a&ility o# !arryin. the "utant C'TR allele. I# either /arent i$ a !arrier the /ro&a&ility that the !hil% 0ill in her it the "utant allele #ro" that /arent i$ 1FG. To inherit the !y$ti! #i&ro$i$ %i$ea$e the !hil% "u$t in%e/en%ently inherit a "utant allele #ro" &oth /arent$. The /ro&a&ility that the "other i$ a !arrier an% that $he 0ill tran$"it the "utant allele i$ 1FH,) 11G an% the /ro&a&ility that the #ather i$ a !arrier an% 0ill tran$"it the "utant allele i$ 1FH,) 1FG. The /ro&a&ility that &oth e:ent$ 0ill o!!ur /ro%u!in. a !hil% 0ith !y$ti! #i&ro$i$ i$ the /ro%u!t o# the /ro&a&ilitie$ o# the$e in%e/en%ent E:ent$ L 11FH,)1FG2 ) 11F1,, ) 1FG2 L 1F1G,,,. E%u!ational O&<e!ti:e= A#ter /arti!i/atin. in thi$ learnin. e)er!i$e you $houl% &e a&le to !al!ulate the /ro&a&ility that a !hil% o# /arent$ #ro" t0o /o/ulation$ 0ith %i##erent "utant allele !arrier #re6uen!ie$ 0ill inherit an auto$o"al re!e$$i:e %i$ea$e.

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Q NO 17: Diru$ A !annot nor"ally in#e!t hu"an e/ithelial !ell$. A#ter e)/o$ure to :iru$ in non9hu"an !ell$5 :iru$ A a!6uire$ the a&ility to in#e!t hu"an e/ithelial !ell$N ho0e:er5 the :iral /arti!le$ .enerate% a$ a re$ult o# thi$ in#e!tion $till !annot in#e!t hu"an e/ithelial !ell$. The /heno"enon %e$!ri&e% i$ &e$t !ate.ori7e% a$ 0hi!h o# the #ollo0in.K A. Rea$$ort"ent . Re!o"&ination C. Tran$#or"ation D. Phenoty/i! "i)in. E. Inter#eren!e

Explanation: The a!6ui$ition o# a ne0 :iral $ur#a!e /rotein i$ o#ten all that i$ ne!e$$ary #or a :iru$ to in#e!t a ne0 ty/e o# ho$t !ell. In the illu$tration a&o:e5 the :iru$ A .eno"e o&tain$ $o"e o# the $ur#a!e !o"/onent$ o# :iru$ 1an% :i!e :er$a2 0hile &oth :iru$e$ are /re$ent $i"ultaneou$ly in the $a"e hu"an !ell. Thi$ e)!han.e i$ %e#ine% a$ /henoty/i! "i)in.5 0hi!h .enerally o!!ur$ 0hen a ho$t !ell i$ !o9in#e!te% &y t0o :iral $train$ an% /ro.eny :irion$ are /ro%u!e% that !ontain nu!leo!a/$i% or en:elo/e /rotein$ #ro" the #ir$t $train an% the .eno"e o# the $e!on% $train 1or :i!e :er$a2. Sin!e :iru$ A a!6uire% $o"e :iru$ $ur#a!e /rotein$ &ut no .eneti! e)!han.e o!!urre%5 the /ro.eny are !on$i%ere% /henoty/i!ally "i)e%. The ne)t .eneration 0ill re:ert to ha:in. only :iru$ A ty/e $ur#a!e /rotein$ 1:iru$ A /henoty/e2 an% 0ill a.ain &e non9in#e!tiou$ #or hu"an e/itheliu". 1Choi!e A2 Rea$$ort"ent re#er$ to !han.e$ in .eno"i! !o"/o$ition that o!!ur 0hen ho$t !ell$ are !o9in#e!te% 0ith t0o $e."ente% :iru$e$ that e)!han.e 0hole .eno"e $e."ent$. Thi$ /ro!e$$ !an !au$e $u%%en alteration$ in the $ur#a!e anti.en$ o# the :iral /ro.eny5 a$ o&$er:e% 0ith the hi.hly "uta.eni! in#luen7a :iru$. When rea$$ort"ent take$ /la!e in a !ell !o9in#e!te% &y t0o :iral $train$ any .eno"i! !han.e in the #ir$t .eneration /ro.eny that i$ re$/on$i&le #or ne0 in#e!ti:ity to hu"an e/ithelial !ell$ 0ill al$o &e /re$ent in the $e!on% .eneration. 1Choi!e 2 Re!o"&ination "ay &e %e#ine% a$ the e)!han.e o# .ene$ &et0een t0o !hro"o$o"e$ 1%ou&le9$tran%e% DNA "ole!ule$2 &y !ro$$in. o:er 0ithin ho"olo.ou$ re.ion$. When re!o"&ination take$ /la!e in a !ell !o9in#e!te% &y t0o :iral $train$ any .eno"i! !han.e in the #ir$t .eneration /ro.eny that i$ re$/on$i&le #or ne0 in#e!ti:ity to hu"an e/ithelial !ell$ 0ill al$o &e /re$ent in the $e!on% .eneration.

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1Choi!e C2 Tran$#or"ation i$ .enerally %e#ine% a$ the u/take o# nake% DNA &y a /rokaryoti! or eukaryoti! !ell. In :irolo.y thi$ ter" "ay al$o &e u$e% to %e$!ri&e the in!or/oration o# :iral DNA into a ho$t !ell !hro"o$o"e. Tran$#or"ation alter$ the .eneti! !o"/o$ition o# the ho$t !ell &ut ty/i!ally !au$e$ no .eno"i! !han.e in /ro.eny :irion$. 1Choi!e E2 Inter#eren!e i$ the inhi&ition &y one :iru$ o# the re/li!ation an%For relea$e o# a $e!on% :iru$ that i$ in#e!tin. the $a"e !ell. Si"/le inter#eren!e 0oul% not re$ult in a ne0 /ro.eny /henoty/e. E%u!ational O&<e!ti:e= Phenoty/i! "i)in. re#er$ to !o9in#e!tion o# a ho$t !ell &y t0o :iral $train$ re$ultin. in /ro.eny :irion$ that !ontain nu!leo!a/$i% /rotein$ #ro" one $train an% the .eno"e o# the other $train. Sin!e there i$ no !han.e in the un%erlyin. :iral .eno"e$ 1no .eneti! e)!han.e2 the ne)t .eneration o# :irion$ re:ert$ to their ori.inal5 un"i)e% /henoty/e$.

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Q NO 18: A G,9year9ol% 0o"an un%er.oe$ a &ilateral oo/hore!to"y. The o:arie$ are $"all an% un%er%e:elo/e%. On li.ht "i!ro$!o/i! e)a"ination5 the o:arie$ are #oun% to !on$i$t o# !onne!ti:e ti$$ue 0ith no #olli!le$ /re$ent. Thi$ /atient i$ at in!rea$e% ri$k #or 0hi!h o# the #ollo0in.= A. Mitral :al:e /rola/$e . Aorti! !oar!tation C. Len$ %i$/la!e"ent D. Da.inal a%eno$i$ E. Pan!reati! in$u##i!ien!y Explanation: The o:arie$ %e$!ri&e% in the :i.nette are the B$treak o:arie$C o# Turner($ $yn%ro"e 1karyoty/e >+ ?O5 la!kin. the /aternal ? !hro"o$o"e2. In Turner($ $yn%ro"e5 the o:arie$ %e:elo/ nor"ally %urin. #etal li#e. ;o0e:er5 la!k o# the /aternal ? !hro"o$o"e !au$e$ lo$$ o# #olli!le$ &y a.e G. At /u&erty5 the$e /atient$ %e:elo/ nor"al /u&i! hair &ut #ail to un%er.o &rea$t %e:elo/"ent or "enar!he %ue to o:arian #ailure. Turner($ $yn%ro"e i$ one o# the "o$t !o""on !au$e$ o# /ri"ary a"enorrhea. Ele:ate% le:el$ o# L; an% ES; are !hara!teri$ti!. Turner($ $yn%ro"e i$ a$$o!iate% 0ith a nu"&er o# e)tra.ona%al a&nor"alitie$5 in!lu%in.= 1. Chara!teri$ti! a//earan!e= $hort $tature5 $hiel% !he$t 1&roa%5 0ith 0i%ely $/a!e% ni//le$25 0e&&e% ne!k 1&roa% ne!k 0ith lo0 hairline2 G. Ly"/he%e"a "ay /re$ent at any a.e. Ly"/he%e"a in the neonate i$ $u..e$ti:e o# Turner($ $yn%ro"e. H. Car%io:a$!ular "al#or"ation$5 in!lu%in. !oar!tation o# the aorta5 &i!u$/i% aorti! :al:e5 an% aorti! %i$$e!tion in a%ulthoo%. 1Choi!e$ A an% C2 Mitral :al:e /rola/$e an% len$ %i$/la!e"ent are $een in /atient$ 0ith Mar#an $yn%ro"e. The$e /atient$ are al$o at ri$k #or aorti! root %ilation an% aorti! %i$$e!tion. 1Choi!e D2 Da.inal a%eno$i$ i$ re/la!e"ent o# the :a.inal $6ua"ou$ e/itheliu" 0ith .lan%ular !olu"nar e/itheliu". It o!!ur$ in the #e"ale !hil%ren o# 0o"en e)/o$e% to %iethyl$til&e$trol 1DES2 %urin. /re.nan!y. Da.inal a%eno$i$ i$ a /re!ur$or o# !lear !ell a%eno!ar!ino"a o# the :a.ina. 1Choi!e E2 Pan!reati! in$u##i!ien!y o!!ur$ in /atient$ 0ith !y$ti! #i&ro$i$. E%u!ational O&<e!ti:e= BStreak o:arie$C a"enorrhea an% in#ertility are the .ona%al "ani#e$tation$ o# Turner($ $yn%ro"e. Thi$ !on%ition i$ a$$o!iate% 0ith $hort $tature 0e&&e% ne!k5 lo0 /o$terior hairline an% !oar!tation o# the aorta.

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Q NO 19: A $till&orn #etu$ %eli:ere% at the G-th 0eek o# .e$tation ha$ #lat #a!ial #eature$ an% e)!e$$i:e $kin at the /o$terior ne!k. Auto/$y #in%in.$ in!lu%e a :entri!ular $e/tal %e#e!t an% %uo%enal atre$ia. Whi!h o# the #ollo0in. i$ the "o$t likely karyoty/e a&nor"ality in thi$ #etu$K Tri$o"y G1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ '. >35 ?@@ G. >+5 ?O

A.

Explanation: 'lat #a!ial #eature$ an% e)!e$$i:e $kin at the na/e o# the ne!k are t0o o# nu"erou$ /henoty/i! #eature$ a$$o!iate% 0ith Do0n $yn%ro"e 1tri$o"yGl2. Other !la$$i! /henoty/i! #in%in.$ in!lu%e $lante% /al/e&ral #i$$ure$ an% a $in.le tran$:er$e /al"ar !rea$e. Di$!eral ano"alie$ are !o""on. Car%ia! %e#e!t$ are #oun% in a//ro)i"ately hal# o# all in#ant$ 0ith Do0n $yn%ro"e5 0ith the en%o!ar%ial !u$hion %e#e!t 1atrio:entri!ular $e/tal %e#e!t2 an% :entri!ular $e/tal %e#e!t "o$t o#ten $een. Ga$trointe$tinal tra!t a&nor"alitie$ are al$o i%enti#ie% in 1,91+4 o# thi$ /atient /o/ulation5 an% !an in!lu%e %uo%enal atre$ia5 ;ir$!h$/run.($ %i$ea$e5 an% tra!heoe$o/ha.eal #i$tula. Do0n $yn%ro"e in!i%en!e in!rea$e$ 0ith "aternal a.e. The :a$t "a<ority o# !a$e$ ari$e %ue to !hro"o$o"al non%i$<un!tion %urin. "aternal "eio$i$ I5 0hi!h re$ult$ in a #ull tri$o"y G1 /re$ent at !on!e/tion. 1Choi!e 2Tri$o"y 1- 1E%0ar%$ $yn%ro"e2 o#ten re$ult$ in #etal %eath. Clini!al "ani#e$tation$ in li:e&orn in#ant$ in!lu%e /ro"inent o!!i/ut "i!ro.nathia5 $"all "outh5 lo09$et an% "al#or"e% ear$5 an% ro!ker9&otto" #eet. Clen!he% han%$ 0ith the in%e) #in.er o:erri%in. the "i%%le #in.er an% the #i#th #in.er o:erri%in. the #ourth #in.er are !hara!teri$ti! #or thi$ !on%ition. 1Choi!e C2Tri$o"y 1H 1Patau $yn%ro"e2 o#ten re$ult$ in #etal %eath. Clini!al "ani#e$tation$ in li:e&orn in#ant$ in!lu%e !le#t li/ an% /alate /oly%a!tyly5 "i!ro!e/haly5 ro!ker9&otto" #eet an% u"&ili!al hernia. Car%ia! an% renal %e#e!t$ are u$ually /re$ent. 1Choi!e$ D5 E5 an% '2 Aaryoty/e$ >35 ???5 >35 ??@ 1Aline#elter $yn%ro"e25 an% >35 ?@@ %o not !au$e %eath in utero. Ne0&orn$ 0ith the$e karyoty/e$ are /henoty/i!ally nor"al 0ith no o&:iou$ %y$"or/hi$". 1Choi!e G2 Still&orn #etu$e$ 0ith Turner $yn%ro"e 1>+?O2 are likely to ha:e e%e"atou$ han%$ an% #eet !y$ti! hy.ro"a o# the ne!k an% !oar!tation o# the aorta. Turner $yn%ro"e i$ not a$$o!iate% 0ith #lat #a!ial #eature$ :entri!ular $e/tal %e#e!t$ or %uo%enal atre$ia E%u!ational O&<e!ti:e= Do0n $yn%ro"e 1tri$o"y G12 o!!ur$ in a//ro)i"ately 1 in 3H, li:e &irth$. The "a<ority o# #etu$e$ 0ith thi$ !hro"o$o"al %e#e!t %ie in utero. The tri/le "arker te$t5 6ua%ru/le "arker te$t5 an% inte.rate% te$t allo0 #or Do0n $yn%ro"e $!reenin.. A"nio!ente$i$ an% !hro"o$o"al analy$i$ o# #etal !ell$ !an &e u$e% to :eri#y the %ia.no$i$.

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Q NO 20: A >,9year9ol% /re.nant #e"ale at G- 0eek$ .e$tation /re$ent$ 0ith :a.inal &lee%in.. There are no #etal heart tone$ au%i&le on Do//ler ultra$oun%. The ti$$ue$ e:a!uate% #ro" the /atient($ uteru$ !on$i$t o# :e$i!le$ an% ha:e a >E ?? .enoty/e. Ti$$ue analy$i$ 0oul% "o$t likely re:eal !hro"o$o"e$ %eri:e%= 'ro" the #ather only . ;al# #ro" the #ather an% hal# #ro" the "other C. Mo$tly #ro" the #ather D. Mo$tly #ro" the "other E. 'ro" the "other only

Explanation: Thi$ /atient ha$ a hy%ati%i#or" "ole. A "ole i$ a #or" o# .e$tational tro/ho&la$ti! %i$ea$e that !an &e !la$$i#ie% a$ !o"/lete or /artial. A !o"/lete "ole ha$ no #etal $tru!ture$ an% i$ !o"/o$e% entirely o# lar.e5 e%e"atou$ an% %i$or%ere% !horioni! :illi that a//ear .ro$$ly a$ !lu$ter$ o# :e$i!ular $tru!ture$ 0ith a B&un!h o# .ra/e$C a//earan!e. Co"/lete "ole$ al"o$t al0ay$ ha:e a >E ?? karyoty/e5 an% all !hro"o$o"e$ are /aternally %eri:e% 1Choi!e A2. A !o"/lete "ole #or"$ 0hen a $/er" #ertili7e$ an e.. an% re/li!ate$ it$ o0n !hro"o$o"e$ 0hile eli"inatin. the "aternal !hro"o$o"e$. RAn%ro.ene$i$( i$ the ter" #or thi$ /ro!e$$ o# #or"ation an% $ur:i:al o# ti$$ue o# !o"/letely /aternal %eri:ation. Unlike in a !o"/lete "ole5 a /artial hy%ati%i#or" "ole $ho0$ #or"ation o# $o"e #etal $tru!ture$ .ro$$ly. A%%itionally5 a /artial "ole ty/i!ally re$ult$ #ro" #ertili7ation o# an o:u" 1one $et o# ha/loi% "aternal !hro"o$o"e$2 &y t0o or "ore $/er" 1t0o $et$ o# ha/loi% /aternal !hro"o$o"e$2 re$ultin. in karyoty/e$ like EJ ??@ or EJ ???. 1Choi!e 2 In "o$t nor"al /re.nan!ie$5 hal# o# the !hro"o$o"e$ are #ro" the #ather an% hal# are #ro" the "other. 1Choi!e$ C an% D2 Con%ition$ !au$e% 0hen a %i$/ro/ortionate a"ount o# !hro"o$o"e$ are either /aternal or "aternal in!lu%e= /artial "olar /re.nan!y5 %i$ea$e$ !au$e% &y !hro"o$o"al non%i$<un!tion $u!h a$ Do0n5 E%0ar%$5 an% Patau $yn%ro"e$5 an% Aline#elter 1??@2 an% ?@@ $yn%ro"e$. E%u!ational O&<e!ti:e= A !o"/lete "ole re$ult$ #ro" #ertili7ation o# an o:u" that i$ %e:oi% o# .eneti! "aterial an% $u&$e6uent re%u/li!ation o# the /aternal .eneti! !o"/le"ent .i:in. a !hara!teri$ti! >E ?? .enoty/e.

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Q NO 21: A G>9year9ol% re!ent Ru$$ian i""i.rant %e$!ri&e$ a lon. hi$tory o# 0ei.ht lo$$5 ni.ht $0eat$ an% na..in. !ou.h. I"a.in. an% &io/$y o# hi$ lun.$ re:eal nu"erou$ a/i!al .ranulo"a$ 0ith !entral !a$eou$ ne!ro$i$. Surroun%in. the ne!roti! area$ are lar.e !ell$ 0ith a&un%ant /ale !yto/la$"= the$e !ell$ "o$t likely ha:e 0hi!h o# the #ollo0in. $ur#a!e "arker$K A. CD> . CD3 C. CDD. CD1> E. CDG, Explanation: Thi$ /atient($ hi$tory o# ni.ht $0eat$5 0ei.ht lo$$5 an% !ou.h to.ether 0ith the #in%in. o# a/i!al /ul"onary .ranulo"a$ $ho0in. !a$eou$ ne!ro$i$ are hi.hly $u..e$ti:e o# $e!on%ary tu&er!ulo$i$. The !a$eatin. .ranulo"a$ o# tu&er!ulo$i$ !on$i$t o# lar.e e/ithelioi% "a!ro/ha.e$ 0ith /ale /ink .ranular !yto/la$" $urroun%in. a !entral re.ion o# ne!roti! %e&ri$. CD> i$ a $ur#a!e "arker o# the "ono!yte9"a!ro/ha.e !ell I"a.e. 1Choi!e A2 To.ether 0ith T9!ell re!e/tor$ CD> tran$"e"&rane /rotein$ re!o.ni7e anti.en$ /re$ente% &y M;C Cla$$ II "ole!ule$. CD> i$ thu$ #oun% on the $ur#a!e o# M;C Il9re$tri!te% T9hel/er !ell$. Althou.h .ranulo"a$ "ay &e $urroun%e% &y a !ollar o# "ononu!lear leuko!yte$5 "ainly ly"/ho!yte$ 1/o$$i&ly in!lu%in. CD>M T9!ell$2 an% $o"e /la$"a !ell$5 the$e are %i$tin!t #ro" the lar.e e/ithelioi% "a!ro/ha.e$ that are al"o$t al0ay$ /re$ent in .ranulo"a$. 1Choi!e 2 CD3 i$ a "ulti9!hain !o"/le) T9!ell "arker. 1Choi!e C2 CD- i$ a tran$"e"&rane /rotein a$$o!iate% 0ith T9!ell re!e/tor$. To.ether the$e /rotein$ re!o.ni7e anti.eni! /e/ti%e$ /re$ente% &y M;C Cla$$ I "ole!ule$. Thu$ CD- i$ #oun% on the $ur#a!e o# M;C I re$tri!te% !ytoto)i! T9!ell$. 1Choi!e E2 CDG, i$ a 9!ell $ur#a!e "arker. Mono!lonal anti&o%ie$ a.ain$t the CD9G, anti.en 1Ritu)i"a&2 ha:e &een $u!!e$$#ul in the treat"ent o# ly"/ho"a$. E%u!ational O&<e!ti:e= The !a$eatin. .ranulo"a$ o# tu&er!ulo$i$ al"o$t al0ay$ !ontain lar.e e/ithelioi% "a!ro/ha.e$ 0ith /ale /ink .ranular !yto/la$" an% $ur#a!e CD1> at the /eri/hery. CD1> i$ a $ur#a!e "arker o# the "ono!yte9"a!ro/ha.e !ell I"a.e. CD> an% CDare $ur#a!e "arker$ o# T9hel/er an% T9killer !ell$ re$/e!ti:ely.

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Q NO 22: A Cau!a$ian "ale /re$ent$ to your o##i!e 0ith "il% hea%a!he$ o# re!ent9 on$et an% le#t le. 0eakne$$. The le$ion$ on /hy$i!al e)a" are $ho0n in the /hoto &elo0.

I# inherite%5 thi$ /atient($ %i$or%er i$ "o$t likely to &e 0hi!h o# the #ollo0in.K A. Sin.le .ene ?9linke% . Sin.le .ene auto$o"al re!e$$i:e C. Sin.le .ene auto$o"al %o"inant D. Mito!hon%rial E. Continuou$ .ene %eletion '. Multi#a!torial Explanation: The "ulti/le $"all !utaneou$ le$ion$ $ho0n in the i"a.e are "o$t likely neuro#i&ro"a$ a$$o!iate% 0ith NE ty/e 1. It i$ an auto$o"al %o"inant !on%ition 0ith hi.h /enetran!e 1"o$t /atient$ 0ho inherit the .ene %e:elo/ the %i$ea$e2. Mutation o# the N'91 .ene5 lo!ate% on !hro"o$o"e 135 i$ re$/on$i&le #or thi$ %i$or%er. The /re$entation o# N'91 i$ hi.hly :aria&le= all or none o# the #ollo0in. $y"/to"$ "ay&e /re$ent in any in%i:i%ual 0ho $u##er$ #ro" N'91. 1. Skin= Ca#S9au9Iait $/ot$ are hy/er/i."ente% le$ion$ 0ith either $"ooth or irre.ular &or%er$. The /re$en!e o# a)illary or in.uinal #re!kle$ i$ another !utaneou$ #eature o# NE9i. G. Neuro#i&ro"a$= $ort5 $e$$ile or /e%un!ulate% le$ion$ that :ary in $i7e. They are !o""only "ulti/le an% %i$tri&ute% throu.hout the &o%y. H. Eye= O/ti! ner:e .lio"a$ "ay o!!ur an% !au$e :i$ual lo$$. Li$!h no%ule$ are /i."ente% ha"arto"a$ o# the iri$ an% are a$y"/to"ati!. >. ony a&nor"alitie$ in!lu%e $/henoi% %y$/la$ia5 !on.enital /$eu%oarthro$i$5 an% $!olio$i$. +. Other a$$o!iate% tu"or$= "enin.io"a$5 .lio"a$5 /heo!hro"o!yto"a$. Thi$ /atient($ hea%a!he$ an% le#t le. 0eakne$$ are /ro&a&ly the re$ult o# a "enin.io"a. E%u!ational O&<e!ti:e= Neuro#i&ro"ato$i$ ty/e l i$ a $in.le9.ene auto$o"al9%o"inant %i$or%er. It o!!ur$ %ue to "utation o# the N'91 .ene lo!ate% on the !hro"o$o"e i 3. Ca#e9au9lait $/ot$5 "ulti/le neuro#i&ro"a$5 an% Li$!h no%ule$ are the "o$t !o""on $y"/to"$.

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Q NO 23: A $till&orn #etu$ %eli:ere% at the GHr% 0eek o# .e$tation i$ #oun% to ha:e an e%e"atou$ ne!k an% &roa% !he$t. Auto/$y re:eal$ aortal !oar!tation5 a &i!u$/i% aorti! :al:e5 an% ki%ney$ that are #u$e% at the "i%line. Whi!h o# the #ollo0in. i$ the "o$t likely karyoty/e a&nor"ality in thi$ #etu$K A. Tri$o"y G1 . Tri$o"y 1C. Tri$o"y 1H D. >35 ??? E. >35 ??@ '. >+5 ?O Explanation: Turner $yn%ro"e 1>+5 ?O2 i$ the likely %ia.no$i$ in a $till&orn #etu$ 0ith nu!hal e%e"a &roa% !he$t5 an% !oar!tation o# the aorta. Mo$t #etu$e$ /o$$e$$in. the >+ ?O karyoty/e a&ort $/ontaneou$ly5 0ith $tu%ie$ $u..e$tin. that 1+4 o# all $/ontaneou$ a&ortion$ are %ue to Turner $yn%ro"e. The "o$t /ro"inent #in%in. in the neonate or #etu$ 0ith Turner $yn%ro"e i$ ly"/he%e"a o# the han%$ an% #eet. A&nor"al nu!hal ly"/ho.ene$i$ !au$e$ $u&!utaneou$ nu!hal e%e"a an% !y$ti! hy.ro"a in utero. The ly"/he%e"a i$ al$o re$/on$i&le #or other !o""on "ani#e$tation$ o# Turner $yn%ro"e5 in!lu%in. the 0e&&e% ne!k an% lo0 /o$terior hair line. Car%ia! a&nor"alitie$ a$$o!iate% 0ith Turner $yn%ro"e in!lu%e !oar!tation o# the aorta an% a &i!u$/i% aorti! :al:e. ;or$e$hoe ki%ney 1#u$ion o# ki%ney$ at the "i%line2 i$ al$o i%enti#ie% in "any Turner $yn%ro"e #e"ale$. In the a%ult5 !la$$i! !lini!al "ani#e$tation$ o# Turner $yn%ro"e in!lu%e $hort $tature5 &roa% $hiel%9like !he$t5 0e&&e% ne!k5 an% /ri"ary o:arian #ailure. The o:arie$ &e!o"e in#iltrate% 0ith #i&rou$ ti$$ue 1B$treak o:arie$C2 an% #ail to /ro%u!e e$tro.en$. 1Choi!e A2 The #etu$ 0ith Do0n $yn%ro"e 1tri$o"y G12 0ill ty/i!ally ha:e a #lat #a!e5 a&nor"al ear$5 $lante% /al/e&ral #i$$ure$5 re%un%ant $kin at the na/e o# the ne!k5 hy/otonia5 /el:i! %y$/la$ia5 an% $in.le tran$:er$e /al"ar !rea$e. 1Choi!e 2 Tri$o"y 1- 1E%0ar%$ $yn%ro"e2 i$ the $e!on% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$. Clini!al "ani#e$tation$ in!lu%e /ro"inent o!!i/ut5 "i!ro.nathia5 $"all "outh5 lo09$et an% "al#or"e% ear$5 an% ro!ker9&otto" #eet. Clen!he% han%$ 0ith the in%e) #in.er o:erri%in. the "i%%le #in.er an% the #i#th #in.er o:erri%in. the #ourth #in.er are !hara!teri$ti! #or thi$ !on%ition. 1Choi!e C2 Tri$o"y 1H 1Patau $yn%ro"e2 i$ the thir% "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$5 an% the "o$t $e:ere. A##e!te% #etu$e$ ty/i!ally ha:e holo/ro$en!e/haly5 "i!ro!e/haly5 /oly%a!tyly an% ro!ker9&otto" #eet. Multi/le #a!ial a&nor"alitie$ 1e.5 hy/otelori$"5 "i!ro/hthal"ia5 !le#t li/5 !le#t /alate5 a&$ent or "al#or"e% no$e2 #re6uently o!!ur. 1Choi!e D2 The >3 ??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% in%i:i%ual$ "ay ha:e $li.htly %e!rea$e% 1, $!ore$. An in!rea$e% ri$k o# $till&irth i$ not a$$o!iate% 0ith thi$ karyoty/e. 1Choi!e E2 The >35 ??@ 1Aline#elter $yn%ro"e2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intelli.en!e. The ty/i!al /atient i$ a tall "ale 0ith .yne!o"a$tia5 $"all te$te$5 an% in#ertility. An in!rea$e% ri$k o# $till&irth i$ not a$$o!iate% 0ith thi$ karyoty/e. E%u!ational O&<e!ti:e= Ly"/he%e"a i$ a !hara!teri$ti! #in%in. in a #etu$ a##li!te% 0ith Turner $yn%ro"e 1>+5 ?O2. The ly"/he%e"a !an :ary in $e:erity5 ran.in. #ro" e%e"a o# the han%$ an% #eet to hy%ro/$ #etali$. Other !o""on #etal Turner $yn%ro"e a&nor"alitie$ in!lu%e !oar!tation o# aorta an% hor$e$hoe ki%ney.

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Q NO 24: A +9year9ol% .irl i$ &rou.ht to the /hy$i!ian &y her "other. The "other tell$ you that the .irl($ $kin &e!o"e$ re% an% $!alin. 0ith only "ini"al $un e)/o$ure. She &e.an to noti!e thi$ /heno"enon 0hen the !hil% 0a$ "onth ol%. No0 the .irl($ $kin i$ thin an% hy/er/i."ente%. The /atient ha$ a #e0 ne:i on her han%$ that ha:e &een ra/i%ly enlar.in.. The %e#e!ti:e .ene in thi$ /atient i$ re$/on$i&le #or A. Re.ulation o# !ell !y!le . Si.nal tran$%u!tion C. DNA e)!i$ion re/air D. DNA "i$"at!h re/air E. Pre:ention o# "i!ro %eletion '. Re.ulation o# a/o/to$i$ Explanation: Thi$ !lini!al :i.nette %e$!ri&e$ the ty/i!al /re$entation o# )ero%er"a /i."ento$u"5 0hi!h literally "ean$ /i."ente% %ry $kin. Thi$ auto$o"al re!e$$i:e 1AR2 !on%ition o!!ur$ %ue to %e!rea$e% a&ility to re/air DNA #ollo0in. %a"a.e &y UD li.ht. The $kin o# a##e!te% in%i:i%ual$ i$ nor"al at &irth. The %i$ea$e "ani#e$t$ %urin. the #ir$t year o# li#e 0ith erythe"a5 $!alin. an% $u&$e6uent hy/er/i."entation an% lenti.o #or"ation on li.ht9e)/o$e% area$ 1e$/e!ially the #a!e2. Later5 the $kin o# a##e!te% area$ $ho0$ atro/hy telan.ie!ta$ia$ an% inter"in.lin. area$ o# hy/o9an% hy/er/i."entation$. Skin "ali.nan!ie$5 in!lu%in. $6ua"ou$ !ell !ar!ino"a5 &a$al !ell !ar!ino"a an% "ali.nant "elano"a5 %e:elo/ a$ early a$ at +9E year$ o# li#e. Nor"ally the re.ion$ o# DNA %a"a.e% &y UD ra%iation are e)!i$e% an% re/la!e%. In )ero%er"a /i."ento$u"5 the .ene$ that !o%e #or :ariou$ DNA re/air en7y"e$ are a&nor"al. I"/air"ent o# DNA re/air re$ult$ %ue to %e#e!t$ in e)!i$ion o# a&nor"al nu!leoti%e$ or %e#e!t$ in re/la!e"ent o# nu!leoti%e$ #ollo0in. e)!i$ion. Other %i$ea$e$ a$$o!iate% 0ith i"/aire% DNA re/air in!lu%e 'an!oni ane"ia 1AR5 hy/er$en$iti:ity to DNA !ro$$9 linkin. a.ent$2 an% loo" $yn%ro"e 1AR5 hy/er$en$iti:ity to UD %a"a.e an% !he"othera/euti! a.ent$2 a"on. other$. 1Choi!e A2 The R& 1retino&la$to"a2 .ene i$ re$/on$i&le #or re.ulation o# the !ell !y!le. The a&nor"al R& /rotein lo$e$ it$ a&ility to arre$t the !ell !y!le in the ,1 /ha$e. Mutation o# R& i$ a$$o!iate% 0ith retino&la$to"a an% o$teo$ar!o"a. 1Choi!e 2 Mutation o# ra$ /rotein i$ #oun% in "any ty/e$ o# !an!er$. Ra$ !o%e$ #or a ,9/rotein that re.ulate$ $i.nal tran$%u!tion. A&nor"al ra$ $ti"ulate$ $i.nal tran$%u!tion lea%in. to unre.ulate% !ell %i:i$ion5 inhi&ite% a/o/to$i$ an% %e!rea$e% !ell a%he$ion. The$e /re%i$/o$e to "ali.nan!y an% "eta$ta$i$. 1Choi!e D2 A&nor"alitie$ o# .ene$ re$/on$i&le #or DNA "i$"at!h re/air are #oun% in /atient$ 0ith here%itary non/oly/o$i$ !olore!tal !an!er 1;NPCC or Lyn!h $yn%ro"e2. The$e /atient$ ha:e hi.her in!i%en!e o# !olore!tal !ar!ino"a an% other "ali.nan!ie$. 1Choi!e$ E an% '2 ?ero%er"a /i."ento$u" i$ not a$$o!iate% 0ith "utation o# .ene$ that /re:ent "i!ro %eletion$ or re.ulate a/o/to$i$ thou.h %y$re.ulation o# a/o/to$i$ ha$ &een i"/li!ate% in "any #or"$ o# hu"an !an!er. E%u!ational O&<e!ti:e= ?ero%er"a /i."ento$u" %e:elo/$ %ue to a %e#e!t in DNA e)!i$ional re/air. Thi$ %i$ea$e i$ !hara!teri7e% &y in!rea$e% $en$iti:ity to UD ra%iation an% a hi.h in!i%en!e o# all #or"$ o# !utaneou$ "ali.nan!y.

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Q NO 25: Tri/le te$t /er#or"e% on a /re.nant 0o"an atl-0eek$ o# .e$tation re:eal$ lo0 le:el$ o# al/ha9#eto/rotein 1A'P2. A"nio!ente$i$ !on#ir"$ the$e #in%in.$. The "other i$ a kno0n al!oholi! an% $"oker. Lo0 A'P le:el$ are a$$o!iate% 0ith 0hi!h o# the #ollo0in. !on%ition$K Turner $yn%ro"e . O"/halo!ele C. Tri$o"y G1 D. 'etal al!ohol $yn%ro"e E. Neural tu&e %e#e!t$

Explanation: Do0n $yn%ro"e i$ the "o$t !o""on !hro"o$o"al a&nor"ality5 an% the $e!on% "o$t !o""on !au$e o# "ental retar%ation. It i$ a$$o!iate% 0ith a%:an!e% "aternal a.e an% !an &e %ia.no$e% /renatally. Tri/le te$t /er#or"e% at 0eek$ 1E91- o# .e$tation %ete!t$ lo0 al/ha9#eto/rotein 1AEP2 le:el$. A #in%in. o# lo0 AEP on tri/le te$t i$ a$$o!iate% 0ith a %ia.no$i$ o# Do0n $yn%ro"e an% i$ there#ore an in%i!ation #or a"nio!ente$i$. Aaryoty/in. o# #etal !ell$ !ontaine% in a"nioti! #lui% !an %ia.no$e Do0n $yn%ro"e. A&out J,4 o# /atient$ 0ith Do0n $yn%ro"e ha:e tri$o"y G1. The /arent$ o# the$e /atient$ are nor"al an% 0ith the a&nor"ality ari$in. a$ a !on$e6uen!e o# "eioti! non9%y$<un!tion 1#ailure o# !hro"o$o"e G1 to %i:i%e %urin. "eio$i$2. Thi$ a&nor"ality o!!ur$ in the o:u" thu$ e)/lainin. the a$$o!iation o# Do0n $yn%ro"e 0ith in!rea$e% "aternal a.e. 1Choi!e 2 O"/halo!ele !au$e$ in!rea$e% APP le:el$ in "aternal $eru" an% a"nioti! #lui%. ;i.h APP i$ al$o a$$o!iate% 0ith .a$tro$!hi$i$5 "ulti/le .e$tation an% neural tu&e %e#e!t$. 1Choi!e E2 Neural tu&e %e#e!t$ are a$$o!iate% 0ith in!rea$e% AEP le:el$ an% in!rea$e% a!etyl!holine$tera$e le:el$ in a"nioti! #lui%. 1Choi!e$ A an% D2 Turner($ $yn%ro"e an% #etal al!ohol $yn%ro"e %o not !au$e a&nor"al AEP le:el$. E%u!ational O&<e!ti:e= 1. Ele:ate% al/ha9#eto/rotein le:el$ are $een in "ulti/le .e$tation neural tu&e %e#e!t$ 1in!lu%in. $/ina &i#i%a anen!e/haly25 an% a&%o"inal 0all %e#e!t$. G. In !ontra$t Do0n $yn%ro"e i$ a$$o!iate% 0ith lo0 al/ha9#eto/rotein le:el$ in "aternal $eru" an% a"nioti! #lui%. The %e#initi:e /renatal %ia.no$i$ i$ "a%e &y karyoty/in. o# #etal !ell$.

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Q NO 26: A "arrie% !ou/le /re$ent$ to your o##i!e #or routine /renatal !oun$elin.. @ou noti!e that the hu$&an% i$ 1G, !" 1>3C2 tall 0ith %i$/ro/ortionately9$hort u//er an% lo0er e)tre"itie$. ;e !annot /ro:i%e #a"ily hi$tory &e!au$e he 0a$ a%o/te%. ;i$ $/ou$e ha$ nor"al !on$titutional #eature$ an% her #a"ily hi$tory i$ in$i.ni#i!ant. They are !on!erne% a&out their un&orn !hil%($ hei.ht. Whi!h o# the #ollo0in. i$ the &e$t re$/on$e to their !on!ern$K A. The ri$k #or the !hil% to &e $hort i$ a&out +,4. . The ri$k %e/en%$ on the "other($ !arrier $tatu$. C. The ri$k %e/en%$ on the !hil%($ .en%er. D. The ri$k #or the !hil% to &e $hort i$ a&out G+4. E. The !on%ition i$ not inherita&le. Explanation: The hu$&an% in thi$ :i.nette ha$ %i$/ro/ortionately9$hort ar"$ an% le.$5 0hi!h $tron.ly $u..e$t$ a!hon%ro/la$ia. The "o$t !o""on %e#e!t in a!hon%ro/la$ia i$ an a!ti:atin. "utation o##i&ro&Ia$t.roth#a!torre!e/tor9H. Patient$ 0ith a!hon%ro/la$ia ha:e a nor"al $/ine len.th5 &ut ha:e $hort li"&$5 a lar.e hea%5 an% $o"eti"e$ a $a%%le no$e. Tran$"i$$ion o# a!hon%ro/la$ia i$ auto$o"al %o"inant. I# one /arent ha$ an a&nor"al auto$o"al .ene5 there i$ a +,4 !han!e that the /arent 0ill tran$"it the .ene to the !hil%5 0hi!h "ean$ a +,4 ri$k that the !hil% 0ill ha:e the %i$ea$e. So"eti"e$ an inherite% auto$o"al %o"inant trait %oe$ not re$ult in the %i$ea$e /henoty/eN thi$ /heno"enon i$ kno0n a$ Bin!o"/lete /enetration.C 1Choi!e$ an% C2 In $e)9linke% %i$or%er$5 the re$/on$i&le .ene i$ lo!ate% on a $e) !hro"o$o"e 1either ? or @2. Mo$t $e)9linke% %i$or%er$ are ?9linke% re!e$$i:e. In ?9 linke% re!e$$i:e %i$or%er$5 0o"en 0ith the %e#e!ti:e .ene 0ill not ha:e the %i$or%er5 &ut 0ill &e B!arrier$.C Wo"en 0ith the a##e!te% ?9linke%5 re!e$$i:e .ene ha$ a +,4 !han!e o# /a$$in. that .ene on to their "ale or #e"ale !hil%ren. The %i##eren!e i$ that "ale !hil%ren only ha:e one ? !hro"o$o"e an% 0ill &e a##li!te% 0ith the %i$or%er. A##e!te% #e"ale !hil%ren 0ill &e %i$ea$e9#ree &ut 0ill &e !arrier$. The !han!e$ &ra !arrier #e"ale to .i:e &irth to an %i$ea$e% #e"ale i$ :irtually ,4N the !han!e$ o# her .i:in. &irth to an a##e!te% "ale !hil% i$ a&out +,4. Male$ !arryin. an ?9linke%5 re!e$$i:e .ene are a##e!te%N their %au.hter$ al0ay$ &e!o"e !arrier$ &ut their $on$ are ne:er a##e!te% 1&e!au$e they %o not re!ei:e an ? !hro"o$o"e #ro" the #ather2. In ?9linke% %o"inant %i$or%er$ &oth "ale$ an% #e"ale$ are a##e!te%. O# the $on$ an% %au.hter$ o# an a##e!te% #e"ale a//ro)i"ately +,4 0ill ha:e the %i$or%er. 'or an a##e!te% "ale all o# hi$ %au.hter$ 0ill &e a##e!te% an% none o# hi$ $on$ 0ill !arry or "ani#e$t the %i$ea$e.

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1Choi!e D2 A&out G+4 o# !hil%ren are a##e!te% in auto$o"al re!e$$i:e %i$or%er$5 i# &oth /arent$ !arry the %e#e!ti:e .ene. A hi$tory o# !on$an.uinity i$ $o"eti"e$ /re$ent in auto$o"al9re!e$$i:e %i$or%er$. Many o# the auto$o"al re!e$$i:e %i$or%er$ are !au$e% &y en7y"ati! %e#i!ien!ie$. In hetero7y.ote$5 the en7y"e a!ti:ity i$ re%u!e% &y only a&out +,4 an a"ount o# en7y"ati! a!ti:ity that i$ u$ually $u##i!ient to /re:ent the o!!urren!e o# %i$ea$e. E%u!ational O&<e!ti:e= A!hon%ro/la$ia i$ an auto$o"al9%o"inant %i$or%er. The tran$"i$$ion o# auto$o"al %i$or%er$ $tati$ti!ally o!!ur$ in +,4 o# the o##$/rin. o# an a##e!te% /arent.

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Q NO 27: A youn. !ou/le 0ho re!ently i""i.rate% #ro" Ea$tern Euro/e &rin.$ their H9year9ol% $on to your o##i!e #or e:aluation o# an e!7e"atou$ ra$h. On e)a" you o&$er:e that the !hil% $ho0$ $i.n$ o# "ental retar%ation an% ha$ a "ou$y o%or. What i$ the likelihoo% that thi$ !ou/le($ ne)t !hil% 0ill &e a##e!te% 0ith the $a"e %i$ea$eK A. Sa"e a$ the .eneral /o/ulation . 1FHG C. 1F1E D. 11E. 1F> '. 1FG Explanation: Mental retar%ation5 e!7e"a5 an% a "ou$y5 "u$ty &o%y o%or are $i.n$ o# /henylketonuria 1PAU2. PAU i$ an auto$o"al re!e$$i:e %i$ea$e !au$e% &y "utation o# the .ene that !o%e #or /henylalanine hy%ro)yla$e. In the Unite% State$5 /henylalanine le:el$ are "ea$ure% in all neonate$ to $!reen #or PAU. e!au$e PAU i$ inherite% in an auto$o"al re!e$$i:e #a$hion5 0e kno0 that &oth o# the /arent$ %e$!ri&e% a&o:e "u$t &e hetero7y.ou$ !arrier$ o# the "utation. The /ro&a&ility that their ne)t !hil% 0ill inherit the %i$ea$e i$ thu$= /1 L /ro&a&ility that the "other tran$"it$ the "utant allele L 1FG /G L /ro&a&ility that the #ather tran$"it$ the "utant allele L 1FG e!au$e the$e are in%e/en%ent e:ent$5 the /ro&a&ility( that a !hil% 0ill inherit a "utant allele #ro" ea!h !arrier /arent i$ e6ual to /1l ) /GL4. E%u!ational O&<e!ti:e= Mental retar%ation5 e!7e"a5 an% a B"ou$yC or "u$ty( &o%y o%or in a to%%ler are $i.n$ o# /henylketonuria 1PAU2. Mo$t in#ant$ 0ith PAU are &orn to t0o hetero7y.ou$ !arrier /arent$. The /ro&a&ility that hetero7y.ou$ !arrier /arent$ 0ill tran$"it an auto$o"al re!e$$i:e %i$ea$e like PRU to a !hil% i$ 3>.

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Q NO 28: A >H9year9ol% "ale i$ &ein. e:aluate% #or /er$i$tent #e:er5 re!urrent .u" &lee%in. an% #ati.ue. 'in%in.$ o# a /eri/heral &loo% $"ear are $ho0n on the $li%e &elo0. Whi!h o# the #ollo0in. !hro"o$o"al a&nor"alitie$ i$ "o$t likely /re$ent in the a##e!te% !ell$K A. t1-N1>2 . t1JNGG2 C. t11+N132 D. t111N1>2 E. 1H69

Explanation: Thi$ /eri/heral &loo% $"ear $ho0$ $e:eral "yelo&la$t$5 0hi!h are lar.e !ell$ 0ith a&un%ant &a$o/hili! !yto/la$". Myelo&la$t$ ha:e a lar.e nu"&er o# !oar$e ro%9 $ha/e% intra!yto/la$"i! .ranule$5 !alle% Auer ro%$5 a #in%in. !hara!teri$ti! o# a!ute "yelo.enou$ leuke"ia 1AML2. AML i$ %i:i%e% into ei.ht ty/e$=

The MH :ariant o# AMLI a!ute /ro"yelo!yti! leuke"ia5 i$ a$$o!iate% 0ith the !yto.eneti! a&nor"ality 11+N 132. Thi$ !yto.eneti! !han.e !au$e$ tran$#er o# the .ene #or retinoi! a!i% re!e/tor al/ha #ro" !hro"o$o"e 1Tto !hro"o$o"e 1+ in a lo!ation a%<a!ent to the PML 1/ro"yelo!yti! leuke"ia2 .ene. 'u$ion o# the$e t0o .ene$ /ro%u!e$ a !hi"eri! .ene /ro%u!t PMLFRARa5 0hi!h !o%e$ #or an a&nor"al retinoi! a!i% re!e/tor. Thi$ a&nor"al #u$ion .ene /ro%u!t inhi&it$ %i##erentiation o# "yelo&la$t$ an% tri..er$ the %e:elo/"ent o# a!ute /ro"yelo!yti! leuke"ia. 1Choi!e A2 t1-N1>2 i$ a$$o!iate% 0ith urkitt ly"/ho"a. ;ere the !9"y! /rotoon!o.ene i$ "o:e% #ro" !hro"o$o"e - to !hro"o$o"e 1>5 0here iti$ lo!ate% a%<a!ent to the .ene #or i""uno.lo&ulin hea:y !hain. Thi$ /la!e"ent in!rea$e$ the

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/ro%u!tion o# the on!o.ene &e!au$e o# the #re6uen!y 0ith 0hi!h the i""uno.lo&ulin .ene i$ tran$!ri&e%. 1Choi!e 2 Tran$lo!ation o# the a&l .ene #ro" !hro"o$o"e J to !hro"o$o"e GG i$ !hara!teri$ti! #or !hroni! "yelo.enou$ leuke"ia 1CML2. t1JNGG2 #or"$ the BPhila%el/hia !hro"o$o"eC an% re$ult$ in the #or"ation o# a ne0 .ene5 &!r9a&l5 0ho$e /ro%u!t ha$ tyro$ine kina$e a!ti:ity. 1Choi!e D2 Mantle !ell ly"/ho"a i$ a 9!ell "ali.nan!y a$$o!iate% 0ith t111N1>2. Thi$ tran$lo!ation re$ult$ in a!ti:ation o# the !y!lin D .ene. 1Choi!e E2 Deletion o# 1H6 i$ one o# the "ole!ular %e#e!t$ $een in !hroni! ly"/ho!yti! leuke"ia 1CLL2. E%u!ational O&<e!ti:e= The /re$en!e o# ro%9$ha/e% intra!yto/la$"i! in!lu$ion$ kno0n a$ Auer ro%$ i$ !hara!teri$ti! o# "any #or"$ o# a!ute "yelo&la$ti! leuke"ia 1AML2. The MS :ariant o# AMLI a!ute /ro"yelo!yti! leuke"ia5 i$ a$$o!iate% 0ith the !yto.eneti! a&nor"ality 11+=132.

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Q NO 29: A GH9year9ol% "ale 0ith a lon. hi$tory o# %iarrhea an% !ra"/y a&%o"inal /ain i$ $u$/e!te% to ha:e ul!erati:e !oliti$. A !olon &io/$y re:eal$ e)ten$i:e in#la""atory !ell in#iltration o# the "u!o$a. In the t0o 0eek$ #ollo0in. the &io/$y5 the /atient($ !on%ition i"/ro:e$5 %e$/ite not re!ei:in. any ne0 treat"ent$. A re/eat &io/$y re:eal$ "arke%ly %e!rea$e% in#la""ation. Whi!h o# the #ollo0in. !ytokine$ "o$t likely !ontri&ute% to thi$ !han.eK A. TN'9P . IL91 C. IL9> D. IL9+ E. IL91, '. IL91G Explanation: E$$entially5 thi$ 6ue$tion a$k$ u$ to i%enti#y 0hi!h o# the li$te% !ytokine$ ha$ anti9 in#la""atory e##e!t$. TG'98 an% "e"&er$ o# the IL91, #a"ily are !urrently !la$$i#ie% a$ anti9in#la""atory !ytokine$. Al"o$t all !ell$ e)/re$$ TG'98 re!e/tor$. TGE98 inhi&it$ ThG ly"/ho!yte %i##erentiation5 !ytoto)i! T9!ell a!ti:itie$5 an% 9!ell i""uno.lo&ulin $e!retion. It "ay al$o $u//re$$ NA !ell$ LAA !ell$5 an% the !ytoto)i!ity o# "ononu!lear /ha.o!yte$. In hu"an$5 "ono!yte$ an% 9!ell$ are the "a<or /ro%u!er$ o# interleukin91, 1IL9 1,2. IL91, inhi&it$ IL9G an% I'N9y /ro%u!tion &y Th1 ly"/ho!yte$5 IL9> an% IL9+ /ro%u!tion &y ThG ly"/ho!yte$5 an% TN'9P an% IL91G /ro%u!tion &y "ono!yte$. It al$o %e!rea$e$ NA !ell I'N9y /ro%u!tion. Moreo:er5 IL91, inhi&it$ "ono!yte M;C !la$$ II an% 3 e)/re$$ion5 i"/airin. the a&ility o# the$e anti.en /re$entin. !ell$ to a!ti:ate Th !ell$. 1 3 /ro:i%e$ the ne!e$$ary !o$ti"ulatory $i.nal.2 In the /re$en!e o# IL91,5 Th ly"/ho!yte$ "ay &e ren%ere% /er"anently tolerant to $/e!i#i! anti.en$. E%u!ational O&<e!ti:e= O# the !ytokine$ relea$e% in the $ettin. o# ti$$ue in<ury5 TGE98 an% IL91, are thou.ht to %o0n re.ulate lo!al !ytokine /ro%u!tion an% in#la""atory rea!tion$ !ontri&utin. to the $y$te"i! a!ute /ha$e re$/on$e. IL915 IL9>5 IL9+5 an% IL91G $ti"ulate lo!al i""une rea!tion$ an% "ay there#ore &e !on$i%ere% /ro9in#la""atory. IL91 al$o a!t$ $y$te"i!ally to /ro"ote #e:er an% other a$/e!t$ o# the a!ute /ha$e re$/on$e.

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Q NO 30: A >9year9ol% Cau!a$ian "ale 0ith re!urrent lo0er lo&e /ul"onal in#iltrate$ i$ #oun% to ha:e hi.h !hlori%e !ontent in hi$ $0eat. Whi!h o# the #ollo0in. a&nor"alitie$ i$ "o$t likely in thi$ /atientK A. I"/aire% $ynthe$i$ o# a tran$"e"&rane /rotein . A&nor"al /o$t9tran$lational /ro!e$$in. o# a tran$"e"&rane /rotein C. De!rea$e% e/ithelial e)/re$$ion o# a nor"al tran$"e"&rane /rotein D. Poor AIP &in%in. &y a tran$"e"&rane /rotein E. De!rea$e% ion !on%u!tion &y a tran$"e"&rane /rotein Explanation: ;i.h $0eat !hlori%e !on!entration i$ #oun% in !y$ti! #i&ro$i$ 1CE2. C' i$ !hara!teri7e% &y /an!reati! in$u##i!ien!y5 $ino/ul"onary in#e!tion$5 an% "ala&$or/tion. The "o$t !o""on CETR .ene a&nor"ality 1#oun% in a//ro)i"ately 3,4 o# !a$e$2 i$ a H9&a$e /air %eletion that re"o:e$ a /henylalanine at a"ino a!i% /o$ition +,- 1*' +,-2. The /henylalanine %eletion !au$e$ a&nor"al #ol%in. an% #ailure o# .ly!o$ylation. The a&nor"al /rotein i$ %e.ra%e% &e#ore it rea!he$ the !ell $ur#a!e. The *'+,- an% "o$t other CETR "utation$ !au$e a !o"/lete a&$en!e o# CETR #ro" the a/i!al "e"&rane o# e)o!rine %u!tal e/ithelial !ell$. E%u!ational O&<e!ti:e= S0eat !hlori%e !on!entration$ o:er E, ""olFL are #oun% in /atient$ 0ith !y$ti! #i&ro$i$ 1C;2 *'+O- i$ the "o$t !o""on C'TR "utation #oun% in /atient$ 0ith CR Thi$ "utation i"/air$ /o$t9tran$lational /ro!e$$in. o# the CRTR .ene tran$!ri/t. The re$ult i$ %e.ra%ation o# the .ene /ro%u!t &e#ore it !an &e tran$/orte% to the !ell $ur#a!e5 !au$in. !o"/lete a&$en!e o# CETR /rotein #ro" the a/i!al "e"&rane o# e)o!rine %u!t e/ithelial !ell$.

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Q NO 31: A 0o"an /re$ent$ to your o##i!e !o"/lainin. o# hair lo$$. She i$ 0orrie% that $he 0ill .o &al% &e!au$e &oth her #ather an% /aternal .ran%"other $u##ere% #ro" &al%ne$$. The "o$t likely inheritan!e /attern o# thi$ !on%ition i$= A. Auto$o"al %o"inant . Auto$o"al re!e$$i:e C. ?9linke% D. Mito!hon%rial E. S/ora%i!

Explanation: Thi$ /atient %e$!ri&e$ a !on%ition 0ith the #ollo0in. inheritan!e /attern= The re% arro0 i%enti#ie$ the !a$e 1/atient2 un%er !on$i%eration. Thi$ /e%i.ree !oul% re/re$ent auto$o"al %o"inant or ?9Linke% %o"inant tran$"i$$ion &e!au$e the %i$ea$e i$ tran$#erre% to &oth "ale an% #e"ale o##$/rin. #ro" &oth "ale an% #e"ale /arent$5 an% all .eneration$ are a##e!te%. The "o$t !o""on ty/e o# hair lo$$ in "ale$ an% #e"ale$ i$ an%ro.eneti! alo/e!ia 1"ale /attern &al%ne$$2. An%ro.eneti! alo/e!ia ha$ auto$o"al %o"inant inheritan!e 0ith :aria&le /enetran!e an% e)/re$$ion. 1Choi!e 2 The !la$$i! /e%i.ree #or auto$o"al re!e$$i:e inheritan!e $ho0$ %i$ea$e %e:elo/"ent in G+4 o# o##$/rin. #ro" t0o a$y"/to"ati! !arrier /arent$. Ty/i!ally only one .eneration i$ a##e!te%. 1Choi!e D2 Con%ition$ /a$$e% &y "ito!hon%rial inheritan!e are tran$"itte% only &y #e"ale$. A##e!te% "ale$ !annot /a$$ the %i$or%er to their o##$/rin.. 1Choi!e E2 y %e#inition5 $/ora%i! !a$e$ %o not #ollo0 an inheritan!e /attern. S/ora%i! !a$e$ o!!ur ha/ha7ar%ly a"on. unrelate% "e"&er$ o# a /o/ulation o:erti"e. 'or e)a"/le there "ay&e a $/ontaneou$ .ene "utation that !au$e$ a $/ora%i! %i$or%er in an in%i:i%ual 0ith no #a"ily hi$tory o# the %i$ea$e. E%u!ational O&<e!ti:e= A /e%i.ree in:ol:in. a #e"ale in%e) !a$e 1/ro&an%25 a##e!te% #ather5 an% a##e!te% /aternal .ran%"other "o$t likely !orre$/on%$ to auto$o"al %o"inant or ?9linke% %o"inant inheritan!e. An%ro.eneti! alo/e!ia i$ the "o$t !o""on !au$e o# hair lo$$ in &oth "ale$ an% #e"ale$ an% i$ .enerally inherite% a$ an auto$o"al %o"inant or /oly.eni! %i$or%er.

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Q NO 32: A 1>9year9ol% Cau!a$ian "ale i$ &rou.ht to your o##i!e &y hi$ "other. She i$ !on!erne% &e!au$e althou.h tall her $on look$ "u!h youn.er than hi$ /eer$ an% $ho0$ no $i.n$ o# R"a$!ulinity.( On /hy$i!al e)a"ination5 the &oy ha$ /oorly9 %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$. ;e i$ una&le to %i$tin.ui$h $"ell$5 &ut ha$ .oo% :i$ual a!uity. Whi!h o# the #ollo0in. /ath0ay$ i$ "o$t likely %e#e!ti:e in thi$ /atientK

A. . C. D. E.

A C D E

Explanation: The "ale !hil% in the :i.nette ha$ %elaye% /u&erty /lu$ ano$"ia5 !on$i$tent 0ith a %ia.no$i$ o# Aall"ann($ $yn%ro"e. Aall"ann($ $yn%ro"e re$ult$ #ro" a #ailure o# GnR;9$e!retin. neuron$ to "i.rate #ro" their ori.in in the ol#a!tory /la!o%e 1$ituate% out$i%e the !entral ner:ou$ $y$te"2 to their nor"al anato"i! lo!ation in the hy/othala"u$. Mo$t o#ten1 the !au$e i$ a "utation in either the AAL91 .ene or the #i&ro&la$t .ro0th #a!tor re!e/tor9i .ene5 0hi!h !o%e #or /rotein$ re6uire% in thi$ "i.ration. Patient$ 0ith Aall"ann($ $yn%ro"e !la$$i!ally ha:e !entral hy/o.ona%i$" an% ano$"ia5 thou.h there "ay &e other "i%line %e#e!t$ a$ 0ell 1e... !le#t li/ or !le#t /alate2. Mo$t o#ten the$e$ /atient$ /re$ent 0ith %elaye% /u&erty. On /hy$i!al e)a"5 the te$te$ are o#ten <u$t 19G "l in :olu"e. There i$ u$ually $o"e /u&i! hair &e!au$e a%renar!he o!!ur$ nor"ally. In Cau!a$ian$ R%elaye% /u&ertyC i$ %e#ine% a$ the a&$en!e or in!o"/lete %e:elo/"ent o# $e!on%ary $e)ual !hara!teri$ti!$ &y a.e 1> in "ale$ an% &y a.e 1G in #e"ale$. Te$ti!ular enlar.e"ent i$ the #ir$t $i.n o# /u&erty in "ale$ an% &rea$t enlar.e"ent i$ the #ir$t $i.n in #e"ale$. The initiation o# /u&erty an% the

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"aintenan!e o# $e!on%ary $e)ual !hara!teri$ti!$ an% #ertility re6uire the !oor%inate% e##ort$ o# the hy/othala"u$1 /ituitary an% .ona%$. Delaye% /u&erty !an re$ult #ro" a %eran.e"ent any0here in thi$ a)i$. 1Choi!e$ 5 C5 D5 an% E2 The$e /ath0ay$ re/re$ent nor"al #ee%&a!k loo/$ &et0een the te$te$ an% the hy/othala"u$ an% /ituitary. Pituitary 'S; $ti"ulate$ /roli#eration o# the $e"ini#erou$ tu&ule$ an% $/er"ato.ene$i$. The $e"ini#erou$ tu&ule$ /ro%u!e inhi&in5 0hi!h #ee%$ &a!k to inhi&it /ituitary I(S; $e!retion. L; #ro" the /ituitary( $ti"ulate$ the inter$titial Ley%i. !ell$ to /ro%u!e te$to$terone1 0hi!h al$o /arti!i/ate$ in #ee%&a!k inhi&ition. E%u!ational O&<e!ti:e= In Aall"ann($ $yn%ro"e5 there i$ an a&$en!e o# GnR; $e!retory neuron$ #ro" the hy/othala"u$ %ue to %e#e!ti:e "i.ration #ro" the ol#a!tory /la!o%e. The$e /atient$ ha:e !entral hy/o.ona%i$" an% ano$"ia.

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Q NO 33: A 1G9year9ol% Cau!a$ian "ale 0ith "o%erate "ental retar%ation an% a %y$"or/hi! #a!e i$ #oun% to ha:e GGE CCC trinu!leoti%e re/eat$ in a .ene lo!ate% on the ? !hro"o$o"e. Whi!h o# the #ollo0in. i$ the "o$t likely !au$e o# thi$ /atient($ !on%itionK A. E)on %eletion . Chro"o$o"al &reak$ C. Gene "ethylation D. I"/aire% intron $/li!in. E. Mi$"at!h re/air %ete!t Explanation: Thi$ /atient ha$ #ra.ile ? $yn%ro"e5 the $e!on% "o$t !o""on !au$e o# inherite% "ental retar%ation in "ale$ a#ter Do0n $yn%ro"e. In%i:i%ual$ 0ith #ra.ile ? $yn%ro"e o#ten ha:e #a!ial %y$"or/hi$" !hara!teri7e% &y a lon. thin #a!e. a /ro"inent #orehea% an% <a0 lar.e /rotru%in. ear$5 an% tooth !ro0%in.. Ma!roor!hi%i$" 1lar.e te$te$2 i$ ty/i!al #or a##e!te% "ale$ an% ty/i!ally o!!ur$ %urin. /u&erty. The .eneti! %e#e!t re$/on$i&le #or #ra.ile ? $yn%ro"e i$ #oun% on the lon. ar" o# the ? !hro"o$o"e in the area !alle% 'a"ilial Mental Retar%ation .ene9i 1EMP12. Nor"ally thi$ .ene ha$ &et0een + an% ++ CGG trinu!leoti%e re/eat$. In%i:i%ual$ 0ith an in!rea$e% nu"&er o# re/eat$ that re"ain$ le$$ than G,, are $ai% to ha:e a R/er"utation.( Patient$ 0ith the /er"utation are ty/i!ally /henoty/i!ally nor"al. R'ull "utation( o!!ur$ 0hen there are "ore than G,, CGG re/eat$ on the 'MR1 .ene. The in!rea$e% nu"&er o# trinu!leoti%e re/eat$ !au$e$ hy/er "ethylation 1Choi!e C2 o# !y$teine &a$e$ in the 'MR1 .ene lea%in. to .ene ina!ti:ation. 'ra.ile ? $yn%ro"e i$ $o na"e% &e!au$e 0hen ly"/ho!yte$ #ro" a##e!te% in%i:i%ual$ are !ulture% in a #olate9 an% thy"i%ine9%e/lete% "e%iu" an% the karyoty/e analy7e% thi$ re.ion o# the ?9!hro"o$o"e a//ear$ !on$tri!te% an% thin 1or #ra.ile2. 1Choi!e$ A an% D2 E)on$ 1BE)/re$$e% !o%on$C2 are !o%in. re.ion$ o# DNA5 a$ !o"/are% to intron$ 0hi!h %o not !arry .eneti! in#or"ation. Intron$ are re"o:e% %urin. intranu!lear "RNA /ro!e$$in.. There are no a&nor"alitie$ o# e)on %eletion in 'ra.ile ? $yn%ro"e. 1Choi!e 2 ?ero%er"a /i."ento$u"5 ata)ia9telan.ie!ta$ia5 'an!oni($ ane"ia5 an% loo"($ $yn%ro"e are %i$ea$e$ !au$e% &y %e#e!t$ in DNA re/air en7y"e$. 1Choi!e E2 De#e!t$ in DNA "i$"at!h re/air .ene$ !au$e Lyn!h $yn%ro"e5 a !on%ition !hara!teri7e% &y an in!rea$e% ri$k o# here%itary non9/oly/o$i$ !olore!tal !an!er 1;NPCC2 an% e)trainte$tinal "ali.nan!ie$. E%u!ational O&<e!ti:e= The #a"ilial "ental retar%ation .ene 1 1'MR12 i$ lo!ate% on the lon. ar" o# the ? !hro"o$o"e. An in!rea$e% nu"&er o# CGG trinu!leoti%e re/eat$ lea%$ to hy/er "ethetoin o# !y$teine &a$e$ an% .ene ina!ti:ation. Thi$ %e#e!t i$ the !au$e o# #ra.ile ? $yn%ro"e5 0hi!h "ani#e$t$ 0ith "ental retar%ation1 #a!ial %y$"or/hi$"5 an% "a!roor!hi%i$".

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Q NO 34: A 1+9year9ol% Cau!a$ian "ale /re$ent$ to your o##i!e 0ith .ait in$ta&ility an% #re6uent #all$. Phy$i!al e)a"ination re:eal$ ky/ho$!olio$i$5 /e$ !a:u$5 an% lo0er9e)tre"ity ata)ia. Po$ition an% <oint $en$ation are al$o i"/aire%. I# the $y"/to"$ %e$!ri&e% are #ro" an inherite% %i$ea$e thi$ /atient i$ "o$t likely to %ie o# 0hi!h o# the #ollo0in.K A. Li:er #ailure . Car%io"yo/athy C. Renal %i$ea$e D. Intra!ranial &lee%in. E. Aorti! %i$$e!tion '. rain tu"or Explanation: 'rie%rei!h ata)ia i$ an auto$o"al re!e$$i:e !on%ition. The /o$terior !olu"n$ an% the $/ino!ere&ellar tra!t$ o# the $/inal !or% $ho0 %e.enerationN an% lo$$ o# the lar.er $en$ory !ell$ o# the %or$al root .an.lia i$ al$o $een. 'rie%rei!h ata)ia /re$ent$ in !hil%ren +91+ year$ ol% a$ .ait ata)ia 1/ro.re$$i:ely $lo0 an% !lu"$y 0alkin.2. A 0i%e9&a$e% .ait 0ith %i##i!ulty "aintainin. &alan!e i$ !hara!teri$ti!. The #ollo0in. $y"/to"$ are a$$o!iate% 0ith 'rie%rei!h ata)ia= 1. Pro.re$$i:e ata)ia o# all #our li"&$5 !au$e% &y !ere&ellar %y$#un!tion5 i$ $een :ery early. De.eneration o# %or$al !olu"n$ lea%$ to lo$$ o# /o$ition an% :i&ration $en$ation. G. ;y/ertro/hi! !ar%io"yo/athy %e:elo/$ in "ore than +,4 o# /atient$. It lea%$ to !ar%ia! arrhyth"ia$ an% !on.e$ti:e heart #ailure 1C;'2. H. Skeletal a&nor"alitie$ in!lu%e ky/ho$!olio$i$5 /e$ !a:u$5 an% ha""ertoe$. >. Dia&ete$ "ellitu$ %e:elo/$ in a&out 1,4 o# the /atient$. Co"/li!ation$ #ro" !ar%io"yo/athy an% &ul&ar %y$#un!tion 1una&le to /rote!t air0ay2 are the "o$t !o""on !au$e$ o# %eath in /atient$ 0ith 'rie%rei!h ata)ia. The !on%ition$ "entione% in the other !hoi!e$ are not a$$o!iate% 0ith 'rie%rei!h ata)ia. 1Choi!e A2 Li:er #ailure i$ a$$o!iate% 0ith Wil$on %i$ea$e. 1Choi!e C2 Ai%ney %i$ea$e i$ a$$o!iate% 0ith /oly!y$ti! ki%ney %i$ea$e5 an% /re$ent$ at later a.e. 1Choi!e D2 Intra!ranial &lee%in. i$ a$$o!iate% 0ith ru/ture o# erry aneury$". 1Choi!e E2 Aorti! %i$$e!tion i$ a$$o!iate% 0ith Mar#an $yn%ro"e. 1Choi!e '2 rain tu"or 1.lio"a2 i$ a$$o!iate% 0ith neuro#i&ro"ato$i$. E%u!ational O&<e!ti:e= 'rie%rei!h ata)ia i$ an auto$o"al re!e$$i:e !on%ition. The "utate% .ene on !hro"o$o"e J ha$ an in!rea$e% nu"&er o# trinu!leoti%e re/eat$. 'rie%rei!h ata)ia i$ o#ten a$$o!iate% 0ith hy/ertro/hi! !ar%io"yo/athy5 %ia&ete$ "ellitu$5 ky/ho$!olio$i$5 an% #oot %e#or"itie$.

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Q NO 35: A "other &rin.$ her 19"onth9ol% $on to the ER &e!au$e he a//ear$ B#lo//yC an% ha$ not &een #ee%in. 0ell. The "other i$ a >-9year9ol% "ulti/ara an% the #a"ily re!ently e"i.rate% #ro" Ea$tern Euro/e. Phy$i!al e)a"ination re:eal$ "il% <aun%i!e an enlar.e% ton.ue5 .eneral hy/otonia an% an u"&ili!al hernia. Whi!h o# the #ollo0in. i$ the "o$t likely !au$e o# thi$ /atient($ !on%itionK ;y/othyroi%i$" . Do0n $yn%ro"e C. otuli$" D. ;ir$!h$/run. %i$ea$e E. Phenylketonuria

A.

Explanation: The in#ant %e$!ri&e% a&o:e %i$/lay$ $y"/to"$ !on$i$tent 0ith !on.enital hy/othyroi%i$". A##e!te% neonate$ a//ear lethar.i!5 #ee% /oorly5 e)hi&it /rolon.e% <aun%i!e5 an% %e"on$trate !on$ti/ation5 "u$!le hy/otonia5 an% a hoar$e !ry. Phy$i!al e)a"ination o# the in#ant 0ith !on.enital hy/othyroi%i$" re:eal$ /ale %ry5 !ool $kinN "y)e%e"a 1e%e"a o# $kin an% $u&!utaneou$ #at2N an% "a!ro.lo$$ia 1lar.e ton.ue2. Coar$e #a!ial #eature$ an% u"&ili!al hernia are !o""only /re$ent a$ 0ell. The$e in#ant$ al$o ha:e an in!rea$e% in!i%en!e o# !on.enital heart %e#e!t$ $u!h a$ ASD an% DSD. T> i$ e$$ential #or nor"al &rain %e:elo/"ent an% "yelination %urin. early li#e1 an% un%ia.no$e% !on.enital hy/othyroi%i$" /ro%u!e$ /ro#oun% an% irre:er$i&le "ental retar%ation. Thi$ !o"/li!ation i$ /re:ente% &y $!reenin. ne0&orn$ #or !on.enital hy/othyroi%i$". 1 y la05 ne0&orn$ are al$o $!reene% #or /henylketonuria an% .ala!to$e"ia.2 1Choi!e 2 In#ant$ 0ith Do0n $yn%ro"e ha:e u/$lantin. /al/e&ral #i$$ure$5 &ilateral e/i!anthal #ol%$5 a #lat na$al &ri%.e an% a lar.e ton.ue. Other !o""on #eature$ are !on.enital heart %e#e!t$5 %uo%enal atre$ia an% ;ir$!h$/run. %i$ea$e. Do0n $yn%ro"e i$ al$o a$$o!iate% 0ith an in!rea$e% ri$k o# leuke"ia. 1Choi!e C2 In#ant &otuli$" a##e!t$ !hil%ren G9E "onth$ o# a.e 0ho are #e% honey. It /re$ent$ 0ith !on$ti/ation an% /oor $u!kin. #ollo0e% &y "u$!le /araly$i$. In#ant &otuli$" ten%$ to &e le$$ $e:ere than a%ult &otuli$". 1Choi!e D2 ;ir$!h$/run. %i$ea$e re$ult$ #ro" the a&nor"al "i.ration o# neural !re$t !ell$ into the re!to$i."oi% !olon lea%in. to an a&$en!e o# .an.lion !ell$ in the a##e!te% 0all. It /re$ent$ 0ith a&%o"inal %i$tention &iliou$ e"e$i$5 an% #ailure to /a$$ "e!oniu". 1Choi!e E2 Phenylketonuria o!!ur$ %ue to an in&orn %e#i!ien!y o# /henylalanine hy%ro)yla$e that lea%$ to an ina&ility to "eta&oli7e /henylalanine. It "ani#e$t$ 0ith %e:elo/"ental %elay "ental retar%ation5 "ou$y &o%y o%or an% #air $kin !olorin.. E%u!ational O&<e!ti:e= Con.enital hy/othyroi%i$" /re$ent$ $oon a#ter &irth 0ith hy/otonia5 /oor #ee%in.5 <aun%i!e5 "a!ro.lo$$ia5 !on$ti/ation an% u"&ili!al hernia. It $houl% &e %ia.no$e% a$ early a$ /o$$i&le to /re:ent the %e:elo/"ent o# "ental retar%ation.

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Q NO 36: A GH9year9ol% "an i$ &ein. e:aluate% #or "yo!loni! e/ile/$y o# re!ent on$et. The e/i$o%e$ are $hort9li:e% an% tri..ere% &y $tartle. Phy$i!al e)a"ination re:eal$ /ro)i"al "u$!le 0eakne$$. Go"ori tri!hro"e $tain o# a "u$!le &io/$y $/e!i"en $ho0$ "u$!le #i&er$ 0ith a &lot!hy re% a//earan!e. No #a"ily hi$tory i$ a:aila&le &e!au$e the /atient i$ a%o/te%. What i$ the /ro&a&ility that thi$ /atient($ one o##$/rin. 0ill inherit the %i$ea$eK A. 1,,4 . 3+4 C. +,4 D. G+4 E. ,4 Explanation: lot!hy re% "u$!le #i&er$ on Go"ori tri!hro"e $tain are !hara!teri$ti! o# the "ito!hon%rial "yo/athie$. In the$e !on%ition$5 a&nor"al "ito!hon%ria a!!u"ulate un%er the $ar!ole""a o# "u$!le #i&er$. The #i&er$ ha:e an irre.ular $ha/e an% $i7e on !ro$$ $e!tion. 'or thi$ rea$on the "ito!hon%rial "yo/athie$ are al$o kno0n a$ the Bre% ra..e% #i&erC %i$ea$e$. Ele!tron "i!ro$!o/y o# the a##e!te% "u$!le re:eal$ an in!rea$e% nu"&er o# enlar.e%5 a&nor"ally $ha/e% "ito!hon%ria. The "o$t i"/ortant "ito!hon%rial "yo/athie$ are "yo!loni! e/ile/$y 0ith ra..e% re% #i&er$ 1MERR'5 %e$!ri&e% in thi$ :i.nette25 Le&er o/ti! neuro/athy 1&lin%ne$$25 an% "ito!hon%rial en!e/halo/athy 0ith $troke9like e/i$o%e$ an% la!ti! a!i%o$i$ 1MELAS2. Ea!h o# the$e %i$ea$e$ i$ the re$ult o# a "ito!hon%rial .ene "utation. The "ito!hon%rial %i$ea$e$ are !au$e% &y "utation$5 %eletion$ or %u/li!ation$ o# "tDNA. e!au$e $/er" "ito!hon%ria %o not /a$$ into the o:u" %urin. #ertili7ation only "aternal "ito!hon%ria are tran$"itte% to the #etu$. Mito!hon%rial %i$ea$e$ there#ore ha:e "aternal inheritan!e. 'or thi$ rea$on the "ale /atient %e$!ri&e% in thi$ :i.nette 0ill not tran$"it the %i$ea$e to hi$ /ro.eny. 1Choi!e 2 No /ure $in.le9.ene inherite% %i$ea$e $ho0$ 3+4 tran$"i$$ion. There "ay &e 3+4 tran$"i$$ion #or a %i$ea$e 0ith :aria&le /enetran!e. In%i:i%ual$ a##e!te% &y a %i$ea$e 0ith auto$o"al %o"inant inheritan!e re!ei:e one !o/y o# the a&nor"al .ene #ro" one /arent. The !han!e that an a##e!te% /er$on 0ill$ tran$"it the %i$ea$e to hi$Fher !hil% i$ +,4 1Choi!e C2 i# the /arent i$ hetero7y.ou$ #or the .i:en %i$ea$e. I# the /arent i$ ho"o7y.ou$5 there i$ a 1,,4 !han!e 1Choi!e A2 o# tran$"i$$ion. 1Choi!e D2 Auto$o"al re!e$$i:e %i$ea$e$ o!!ur 0hen the in%i:i%ual inherit$ t0o !o/ie$ o# the "utate% .ene 1one #ro" ea!h /arent2. I# &oth /arent$ are !arrier$1 there i$ a G+4 !han!e that the !hil% 0ill &e a##e!te%. E%u!ational O&<e!ti:e= BRe% ra..e%C "u$!le #i&er$ are $een in "ito!hon%rial %i$ea$e$. Mu$!le #i&er$ ha:e thi$ a//earan!e &e!au$e a&nor"al "ito!hon%ria a!!u"ulate un%er the $ar!ole""a. Mito!hon%rial %i$ea$e$ $ho0 "aternal inheritan!e.

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Q NO 37: A GH9year9ol% a$y"/to"ati! "ale /arti!i/ate$ in !lini!al re$ear!h an% i$ #oun% to &e ho"o7y.ou$ #or the a/oli/o/rotein E9> allele. In the #uture5 thi$ /atient i$ "o$t likely to $u##er #ro" 0hi!h o# the #ollo0in.K A. 'a"ilial hy/er!hole$terole"ia . ;y/ertro/hi! !ar%io"yo/athy C. Dia&ete$ "ellitu$5 ty/e G D. Pe/ti! ul!er %i$ea$e E. Poly!y$ti! ki%ney %i$ea$e '. Al7hei"er %e"entia Explanation: Al7hei"er %i$ea$e ha$ a $tron. .eneti! /re%i$/o$ition. A&out H,4 o# /atient$ ha:e a #a"ily hi$tory o# the %i$ea$e. A!!or%in. to a.e 0hen $y"/to"$ &e.in1 Al7hei"er %i$ea$e !an &e !la$$i#ie% a$ early or late. The #ollo0in. three "utation $ite$ ha:e &een a$$o!iate% 0ith early9on $et #a"ilial Al7hei"er %i$ea$e 1on$et U E, year$ ol%2= 1. A"yloi% /re!ur$or /rotein 1APP2 .ene on !hro"o$o"e G1 G. Pre$enilin 1 .ene on !hro"o$o"e 1> H. Pre$enilin G .ene on !hro"o$o"e 1 oth APP an% /re$enilin .ene "utation$ are thou.ht to /ro"ote the /ro%u!tion o# A H9a"yloi%. Late9on $et #a"ilial Al7hei"er %i$ea$e i$ a$$o!iate% 0ith the E> allele o# A/oli/o/rotein E. The e)a!t "e!hani$" o# it$ in#luen!e i$ not kno0n. It i$ thou.ht that the A/oE> /rotein "ay&e in:ol:e% in the #or"ation o# $enile /la6ue$. 1Choi!e A2 'a"ilial hy/er!hole$terole"ia i$ an auto$o"al %o"inant %i$or%er. It i$ a$$o!iate% 0ith a %e#e!t in lo0 %en$ity li/o/rotein 1LDL2 re!e/tor$. Thi$ %e#e!t lea%$ to %e!rea$e% he/ati! LDL u/take an% $e:ere ele:ation in total !hole$terol an% LDL le:el$. 1Choi!e 2 ;y/ertro/hi! !ar%io"yo/athy i$ a #a"ilial %i$or%er inherite% a$ an auto$o"al %o"inant trait. The "o$t !o""on "utation i$ o# the H9"yo$in hea:y !hain. 1Choi!e C2 Geneti! #a!tor$ /lay an i"/ortant role in %ia&ete$ "ellitu$ ty/e G 1"ore i"/ortant than in ty/e 12. Geneti! /re%i$/o$ition to in!rea$e% in$ulin re$i$tan!e an% %eran.e% in$ulin $e!retion &y 1H9!ell$ are i"/ortant /re!ur$or$ to %i$ea$e. 1Choi!e D2 Pe/ti! ul!er %i$ea$e i$ $tron.ly a$$o!iate% 0ith ;. /ylon in#e!tion5 &ut not A/o'>. 1Choi!e E2 Poly!y$ti! ki%ney %i$ea$e !an &e inherite% a$ auto$o"al re!e$$i:e 1al$o !alle% in#antile #or"2 or %o"inant trait 1a%ult #or"2. Neither o# the$e !on%ition$ i$ a$$o!iate% 0ith A/o'>. E%u!ational O&<e!ti:e= Early9on$et #a"ilial Al7hei"er %i$ea$e i$ a$$o!iate% 0ith three .ene "utation$= APP 1!hro"o$o"e G125 /re$enilin 1 an% /re$enilin G. Late9on$et #a"ilial Al7hei"er %i$ea$e i$ a$$o!iate% 0ith a/oli/o/rotein '> .enoty/e.

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GENETICS

Q NO 38: A +9year9ol% "ale $u##er$ #ro" re!urrent %iarrhea that %oe$ not re$/on% to $hort9ter" anti&ioti! thera/y. Li.ht "i!ro$!o/y o# re/eate% %uo%enal a$/irate$ !on$i$tently re:eal$ the #ollo0in.=

Whi!h o# the #ollo0in. "ay &e i"/aire% in thi$ /atientK A. Eo$ino/hil9"e%iate% !ytoto)i!ity . CD-M T ly"/ho!yte9"e%iate% !ytoto)i!ity C. a!terial killin. &y neutro/hil$ D. Me"&rane atta!k !o"/le) #or"ation E. I.A /ro%u!tion Explanation: The a&o:e /i!ture $ho0$ a Giar%ia la"&lia tro/ho7oite. Giar%ia i$ /ear9$ha/e%5 &ilaterally $y""etri! or.ani$"$ 0ith #our /air$ o# #la.ella an% t0o nu!lei. Se!retory I.A hel/$ /re:ent an% !lear in#e!tion &y &in%in. to tro/ho7oite$ an% i"/airin. their a%heren!e to the u//er $"all &o0el "u!o$a. Patient$ %e#i!ient in I.A anti&o%ie$ a.ain$t $/e!i#i! Giar%ia anti.en$ are /rone to !hroni! .iar%ia$i$. Chil%ren 0ith ?9 linke% a.a""a.lo&uline"ia an% /atient$ 0ith !o""on :aria&le i""une %e#i!ien!y ha:e a %o!u"ente% /re%i$/o$ition to .iar%ia$i$. The$e /atient$ al$o ten% to ha:e a /rolon.e% %i$ea$e !our$e 0ith %iarrhea "ala&$or/tion :illu$ #lattenin. !ry/t hy/ertro/hy5 an% %en$e $u&"u!o$al "ononu!lear !ell in#iltrate$ on $"all &o0el &io/$y. 1Choi!e A2 Eo$ino/hil9"e%iate% !>oto)i!it$I i$ not in:ol:e% in the %e#en$e a.ain$t Giar%ia. Rather5 thi$ "e!hani$" i$ i"/ortant in !o"&atin. hel"inthi! in#e!tion$. Eo$ino/hil$ %a"a.e hel"inth lar:ae :ia an anti&o%y %e/en%ent !ellular !ytoto)i!ity 1ADCC2 "e!hani$" /o$$i&ly in:ol:in. "a<or &a$i! /rotein. E%u!ational O&<e!ti:e= Giar%ia Ia"&lia !au$e$ in<ury to the %uo%enal an% <e<unal "u!o$a &y a%herin. to the inte$tinal &ru$h &or%er an% relea$in. "ole!ule$ that in%u!e a "u!o$al in#la""atory re$/on$e. Se!retory I.A5 0hi!h i"/air$ a%heren!e5 i$ the "a<or !o"/onent o# a%a/ti:e i""unity a.ain$t G. la"&lia in#e!tion. Se:ere I.A %e#i!ien!y /re%i$/o$e$ /atient$ to !hroni! .iar%ia$i$.

206

USMLE WORLD STEP 1 Q NO 39: A 1>9year9ol% "ale i$ %ia.no$e% 0ith "il% "ental retar%ation. Cyto.eneti! $tu%ie$ $ho0 a $"all .a/ near the ti/ o# the lon. ar" o# the ? !hro"o$o"e. Phy$i!al e)a"ination o# thi$ /atient i$ likely to $ho0= $tature5 &roa% !he$t5 an% a"enorrhea . Tall $tature5 .yne!o"a$tia5 in#ertility C. Ma!roor!hi%i$"5 lar.e <a0 an% ear$ D. Ara!hno%a!tyly5 $!olio$i$5 len$ %i$lo!ation E. Short &roa% han%$5 tran$:er$e /al"ar !rea$e

GENETICS

A. Short

Explanation: 'ra.ile ? $yn%ro"e i$ the $e!on% "o$t !o""on !au$e o# !on.enital "ental retar%ation a#ter Do0n $yn%ro"e. It i$ inherite% in an ?9linke% #a$hion. The %e#e!t i$ an in!rea$e% nu"&er o# trinu!leoti%e re/eat$ 1CGG2 in the #a"ilial "ental retar%ation .ene 1'MR912 lo!ate% on the lon. ar" o# the ?9!hro"o$o"e. When the !ell$ o# a##e!te% in%i:i%ual$ are !ulture% in #olate9%e#i!ient "e%iu"5 the area o# in!rea$e% re/eat$ %oe$ not $tain an% a//ear$ B&roken Bhen!e the na"e B#ra.ile ?.C Patient$ 0ith #ra.ile ? $yn%ro"e %i$/lay the #ollo0in. #eature$= 1. o%y ha&itu$= Ma!ro$o"ia 0ith in!rea$e% hea% !ir!u"#eren!e "ay &e /re$ent at &irth. Ol%er /atient$ ha:e %y$"or/hi! #a!ial #eature$ in!lu%in. lar.e <a05 lar.e /rotru%in. ear$5 lon. thin #a!e an% /ro"inent #orehea%. Po$t/u&ertal "ale$ in:aria&ly ha:e "a!roor!hi%i$" 1enlar.e% te$te$2. G. Co.niti:e i"/air"ent= e!o"e$ e:i%ent alter the 1$t year o# li#e. Patient$ %e"on$trate "il%9to9"o%erate "ental retar%ation5 $e:ere lan.ua.e %elay an% &eha:ioral a&nor"alitie$ 1$u!h a$ a..re$$i:ene$$2. Auti$ti! #eature$ are "ore !o""on in !hil%ren 0ith #ra.ile ? $yn%ro"e than in the .eneral /o/ulation. 1Choi!e A2 Short $tature5 &roa% 1$hiel%2 !he$t5 0e&&e% ne!k an% lo0 hair line are $i.n$ o# Turner($ $yn%ro"e 1>+ ?O2. A##e!te% #e"ale$ ha:e /ri"ary a"enorrhea %ue to la!k o# e$tro.en $e!retion &y un%er%e:elo/e% 1B$treakC2 o:arie$. 1Choi!e 2 Aline#elter $yn%ro"e 1>3 ??@2 a##e!t$ only "ale$. Patient$ ha:e tall $tature1 .yne!o"a$tia an% $"all5 #ir" te$te$. De!rea$e% te$to$terone $e!retion &y #i&roti! te$te$ !au$e$ oli.o$/er"ia an% in#ertility. 1Choi!e D2 In Mar#an $yn%ro"e there i$ o#ten ara!hno%a!tyly5 $!olio$i$5 an% aorti! root %ilation. Other a$$o!iate% a&nor"alitie$ in!lu%e len$ %i$lo!ation 1e!to/ia lenti$2 an% "itral :al:e /rola/$e. 1Choi!e E2 Short &roa% #in.er$ an% tran$:er$e /al"ar !rea$e are $een in Do0n $yn%ro"e. E%u!ational O&<e!ti:e= 'ra.ile ? $yn%ro"e i$ a !o""on !au$e o# inherite% "ental retar%ation. The %i$or%er i$ ?9linke% an% a##e!t$ "ale$. Patient$ ha:e "ental retar%ation5 %y$"or/hi! #a!ial #eature$ 1lar.e <a0 lar.e /rotru%in. ear$2 an% "a!roor!hi%i$".

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Q NO 40: A HG9year9ol% "ale 0ith Do0n $yn%ro"e e)/erien!e$ $i.ni#i!ant !o.niti:e %e!line5 "akin. hi" totally %e/en%ant on a !are.i:er #or hi$ &a$i! %aily a!ti:itie$. Corti!al neuron$ in thi$ /atient are "o$t likely to %e"on$trate 0hi!h o# the #ollo0in.K A. Pi!k &o%ie$ . Neuro#i&rillary tan.le$ C. Le0y &o%ie$ D. S/on.i#or" tran$#or"ation E. Ne.ri &o%ie$ '. P$a""ona &o%ie$ Explanation: Do0n $yn%ro"e 1tri$o"y G12 i$ the "o$t !o""on !hro"o$o"al ano"aly. Ty/i!al $y"/to"$ are "ental retar%ation an% B"on.oloi%C a//earan!e. Chara!teri$ti! #a!ial #eature$ in!lu%e #lat #a!ie$5 e/i!anthi! #ol%$ an% o&li6ue /al/e&ral #i$$ure$. Patient$ 0ith Do0n $yn%ro"e are un#ortunately "ore /rone to a nu"&er o# "e%i!al /ro&le"$. 'or in$tan!e5 /atient$ 0ith Do0n $yn%ro"e ha:e an in!rea$e% ri$k o# early9on$et Al7hei"er %i$ea$e. eyon% >,5 the$e /atient$ in:aria&ly %e:elo/ $enile /la6ue$ an% neuro #i&rillary tan.le$. The a$$o!iation o# Do0n $yn%ro"e an% Al7hei"er %i$ea$e "ay&e e)/laine% &y the #a!t that the APP .ene i$ lo!ate% on !hro"o$o"e G15 Clea:a.e o# APP 1a"yloi% /re!ur$or /rotein2 #or"$ A 89a"yloi%5 0hi!h i$ the $u&$tan!e that a!!u"ulate$ in &rain ti$$ue an% :e$$el 0all$. Tri$o"y o# G1 entail$ that three !o/ie$ o# the APP .ene are /re$ent. More APP i$ there#ore /ro%u!e% in Do0n $yn%ro"e5 #a!ilitatin. a!!elerate% a!!u"ulation o# a"yloi% an% Al7hei"er9like !han.e$. Other !on%ition$ a$$o!iate% 0ith Do0n $yn%ro"e in!lu%e= 1. A!ute leuke"ia$= &oth AML an% ALL. G. Con.enital heart %i$ea$e= en%o!ar%ial !u$hion %e#e!t$5 DSDI ASD. H. Ga$trointe$tinal %e#e!t$= %uo%enal atre$ia an% ;ir$!h$/run. %i$ea$e. 1Choi!e A2 Pi!k &o%ie$ are eo$ino/hili!5 intra!yto/la$"i! in!lu$ion$ #oun% in the !orti!al neuron$ in Pi!k %i$ea$e. Do0n $yn%ro"e i$ not a$$o!iate% 0ith in!rea$e% ri$k o# Pi!k %i$ea$e. 1Choi!e C2 Le0y &o%ie$ are roun%5 eo$ino/hili!5 intra!yto/la$"i! in!lu$ion$ that !ontain neuro#ila"ent$. They are $een in the neuron$ o# $u&$tantia ni.ra in Parkin$on %i$ea$e. 1Choi!e D2 S/on.i#or" tran$#or"ation i$ !hara!teri$ti! o# Creut7#el%t9Va!o& %i$ea$e5 0hi!h "ani#e$t$ &y ra/i%ly /ro.re$$i:e %e"entia an% "yo!loni! <erk$. Thi$ !on%ition "ay ha:e an in#e!tiou$ etiolo.y an% i$ not a$$o!iate% 0ith Do0n $yn%ro"e. 1Choi!e E2 Ne.ri &o%ie$ are #oun% in /atient$ 0ith ra&ie$ in#e!tion. They are roun%5 eo$ino/hili! in!lu$ion$ $een in the !yto/la$" o# /yra"i%al neuron$ o# the hi//o!a"/u$ an% !ere&ellar Purkin<e !ell$. Ne.ri &o%ie$ !ontain the ra&ie$ :iru$. 1Choi!e '2 P$a""o"a &o%ie$ are la"inar !al!i#i!ation$ #oun% in a nu"&er o# tu"or$ 1"enin.io"a$5 /a/illary thyroi% !ar!ino"a$5 an% "any other$2. E%u!ational O&<e!ti:e= A 89a"yloi% /lay$ an i"/ortant role in the %e:elo/"ent o# Al7hei"er %i$ea$e. It$ /re!ur$or /rotein 1APP2 i$ !o%e% &y a .ene lo!ate% on !hro"o$o"e G1. Patient$ 0ith tri$o"y G1 1Do0n $yn%ro"e2 are likely to %e:elo/ Al7hei"er %i$ea$e a#ter a.e >,.

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Q NO 41: A 1G9year9ol% Cau!a$ian #e"ale i$ &rou.ht to your o##i!e !o"/lainin. o# %i##i!ulty 0alkin.. Phy$i!al e)a"ination re:eal$ #e"oral /ul$e$ that are %elaye% relati:e to the &ra!hial /ul$e$5 an% /ul$atile :e$$el$ alon. her ri&$ an% a)illa. Thi$ /atient($ !on%ition i$ "o$t likely a$$o!iate% 0ith= A. Aarta.ener $yn%ro"e . Tu&erou$ $!lero$i$ C. DiGeor.e $yn%ro"e D. 'rie%rei!h($ ata)ia E. Mar#an $yn%ro"e '. Do0n $yn%ro"e G. Turner($ $yn%ro"e Explanation: Di"ini$he% #e"oral /ul$e$ !o"/are% to &ra!hial /ul$e$5 $y"/to"$ o# ina%e6uate /er#u$ion o# the lo0er e)tre"itie$ %urin. a"&ulation5 an% enlar.e% inter!o$tal arterie$ in a !hil%Fyoun. a%ult are !hara!teri$ti! o# a%ult9ty/e !on.enital !oar!tation o# the aorta. Turner $yn%ro"e 1an ?O $e) !hro"o$o"e %i$or%er2 i$ a$$o!iate% 0ith !oar!tation o# the aorta in .irl$. 1Choi!e A2 In Aarta.ener $yn%ro"e5 !ilia are i""otile %ue to a "i!rotu&ular %ynein ar" %e#e!t. In#ertility5 re!urrent $inu$iti$5 an% &ron!hie!ta$i$ re$ult. Thi$ $yn%ro"e i$ a$$o!iate% 0ith $itu$ in:er$u$5 &ut i$ not kno0n to &e a$$o!iate% 0ith aorti! !oar!tation. 1Choi!e 2 Tu&erou$ $!lero$i$ i$ an auto$o"al %o"inant $yn%ro"e !hara!teri7e% &y !utaneou$ an.io#i&ro"a$ 1a%eno"a $e&a!eu"25 $ei7ure$5 an% "ental retar%ation. Patholo.i!al le$ion$ in!lu%e !entral ner:ou$ $y$te" ha"arto"a$ an% &eni.n neo/la$"$5 renal an% other :i$!eral !y$t$5 a :ariety o# other ha"arto"a$5 an% !ar%ia! rha&%o"yo"a$. 1Choi!e C2 DiGeor.e $yn%ro"e i$ a$$o!iate% 0ith at lea$t 1+4 o# !a$e$ o# interru/te% aorti! ar!h5 a "ore e)tre"e ano"aly than aorti! !oar!tation in 0hi!h the aorti! ar!h i$ atreti! ora $e."ent o# the ar!h i$ a&$ent. In a%%ition to /oor lo0er e)tre"ity /ul$e$ re$/iratory %i$tre$$ :aria&le !yano$i$ an% $i.n$ o# !on.e$ti:e heart #ailure %e:elo/ %urin. the #ir$t %ay$ o# li#e. 1Choi!e D2 'rie%rei!h($ ata)ia i$ "arke% &y $/ino!ere&ellar %e.eneration 0ith /re%o"inantly $/inal ata)ia. Thi$ !an /ro%u!e %i##i!ulty 0alkin.5 &ut #e"oral /ul$e$ are not a##e!te%. Thi$ auto$o"al re!e$$i:e !on%ition i$ a$$o!iate% 0ith hy/ertro/hi! !ar%io"yo/athy. 1Choi!e E2 Mar#an $yn%ro"e i$ a$$o!iate% 0ith !y$ti! "e%ial ne!ro$i$ o# the !o%e5 0hi!h "ay re$ult in %i$$e!tin. aorti! aneury$"$ an% aorti! :al:e in!o"/eten!e. Mitral :al:e /rola/$e "ay al$o re$ult. 1Choi!e '2 Do0n $yn%ro"e i$ a$$o!iate% 0ith en%o!ar%ial !u$hion %e#e!t$ that re$ult in o$tiu" /ri"u" atrial $e/tal %e#e!t$ 1ASD2 an% re.ur.itant atrio:entri!ular :al:e$. E%u!ational O&<e!ti:e= Di"ini$he% #e"oral /ul$e$ !o"/are% to &ra!hial /ul$e$5 $y"/to"$ o# ina%e6uate /er#u$ion o# the lo0er e)tre"itie$ %urin. a"&ulation5 an% enlar.e% inter!o$tal arterie$ in a !hil%Fyoun. a%ult are ty/i!al o# a%ult9ty/e !on.enital !oar!tation o# the aorta. Turner($ $yn%ro"e i$ a$$o!iate% 0ith !oar!tation o# the aorta in .irl$. A :ariety o# other auto$o"al an% $e) !hro"o$o"al inherite% %i$or%er$ are a$$o!iate% 0ith !ar%io:a$!ular %e:elo/"ental %e#e!t$ an%For /atholo.y. The "a<or a$$o!iation$ are a$ #ollo0$=

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W Do0n $yn%ro"e= en%o!ar%ial !u$hion %e#e!t$ 1o$tiu" /ri"u" ASDI re.ur.itant atrio:entri!ular :al:e$2 W DiGeor.e $yn%ro"e= tetralo.y o# 'allot an% interru/te% aorti! ar!h W 'rie%rei!h($ ata)ia= hy/ertro/hi! !ar%io"yo/athy W Mar#an $yn%ro"e= !y$ti! "e%ial ne!ro$i$ o# the aorta W Tu&erou$ $!lero$i$= :al:ular o&$tru!tion %ue to !ar%ia! rha&%o"yo"a$

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Q NO 42: A /atient i$ $u$/e!te% o# ha:in. an inherite% %i$or%er. Pe%i.ree analy$i$ $ho0$ the #ollo0in. /attern 1$ee the $li%e &elo02.

Thi$ /atient i$ "o$t likely to &e $u##erin. #ro" 0hi!h o# the #ollo0in. !on%ition$K A. ;e"o/hilia . ;untin.ton($ %i$ea$e C. Cla$$i!al .ala!to$e"ia D. Le$!h9Nyhan $yn%ro"e E. Le&er here%itary o/ti! neuro/athy Explanation: Ea!h o# the a##e!te% in%i:i%ual$ on thi$ /e%i.ree ha$ inherite% the %i$or%er #ro" a$y"/to"ati! /arent$5 !on$i$tent 0ith an auto$o"al re!e$$i:e inheritan!e /attern. Cla$$i!al .ala!to$e"ia i$ an auto$o"al re!e$$i:e %i$ea$e. Patient$ 0ith .ala!to$e"ia are ho"o7y.ou$ #or a %e#e!ti:e .ala!to$e919/ho$/hate uri%yltran$#era$e .ene. In .eneral5 "o$t en7y"e %e#i!ien!y !on%ition$ #ollo0 an auto$o"al re!e$$i:e inheritan!e /attern5 0herea$ %i$ea$e$ %ue to %e#e!ti:e non9!atalyti! /rotein$ ten% to #ollo0 an auto$o"al %o"inant /attern. 1Choi!e A2 ;e"o/hilia i$ an ?9linke% re!e$$i:e 'a!tor I? %e#i!ien!y that a##e!t$ "ale$. 1Choi!e 2 ;untin.ton($ %i$ea$e i$ inherite% in an auto$o"al %o"inant #a$hion. A##e!te% in%i:i%ual$ .enerally ha:e one a##e!te% /arent. In thi$ !on%ition5 there i$ %e.eneration o# the $triatu" 1"ainly the !au%ate nu!leu$ an% /uta"en2. 1Choi!e D2 Le$!h9Nyhan $yn%ro"e i$ an ?9linke% re!e$$i:e %e#i!ien!y o# hy/o)anthine /ho$/hori&o$yltran$#era$e5 the en7y"e that /ro"ote$ !on:er$ion o# hy/o)anthine to IMP an% .uanine to GMP 1/urine $al:a.e2. 1Choi!e E2 Le&er here%itary o/ti! neuro/athy #ollo0$ a "ito!hon%rial inheritan!e /attern. E%u!ational O&<e!ti:e= On a:era.e auto$o"al re!e$$i:e !on%ition$ a##e!t G+4 o# o##$/rin. o# a$y"/to"ati! hetero7y.ou$ !arrier /arent$. Cla$$i!al .ala!to$e"ia i$ an auto$o"al re!e$$i:e %i$ea$e.

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Q NO 43: An in#ant &orn to a H+9year9ol% #e"ale ha$ a #lat na$al &ri%.e an% a $"all "outh. Aaryoty/e analy$i$ on the in#ant re:eal$ the #ollo0in.=

The /atient i$ "o$t likely to $u##er #ro" 0hi!h o# the #ollo0in. !on%ition$K A. I""otile !ilia . Ma!roor!hi%i$" C. Ri!ket$ D. Re% &loo% !ell $i!klin. E. A!ute ly"/ho&la$ti! leuke"ia '. Chroni! "yelo.enou$ leuke"ia Explanation: Thi$ karyoty/e $ho0$ tri$o"y G1 1>3??5 MG12 in%i!atin. a %ia.no$i$ o# Do0n $yn%ro"e5 the "o$t !o""on !au$e o# !on.enital "ental retar%ation. In "o$t !a$e$5 Do0n $yn%ro"e re$ult$ #ro" "eioti! non%i$<un!tion in the o:u"N the /arent$ are .enerally .eneti!ally nor"al. A##e!te% in%i:i%ual$ "ay e)hi&it a $i"ian !rea$e5 a&un%ant ne!k $kin5 /ro"inent e/i!anthal #ol%$5 a #lat #a!ial /ro#ile5 "ental retar%ation5 a !le#t /alate5 !on.enital heart %i$ea$e5 inte$tinal atre$ia5 hy/otonia5 an%For a .a/ &et0een the #ir$t an% $e!on% toe$. In%i:i%ual$ 0ith Do0n $yn%ro"e ha:e a G,9>, #ol% in!rea$e% ri$k o# %e:elo/in. a!ute ly"/ho&la$ti! leuke"ia 1ALL2. 1Choi!e A2 I""otile !ilia are #oun% in Aarta.ener $yn%ro"e5 a !on%ition !au$e% in "o$t !a$e$ &y an auto$o"al re!e$$i:e "utation in the .ene !o%in. #or the "i!rotu&ule a$$o!iate% /rotein5 %ynein. Male in#ertility5 re!urrent $inu$iti$5 an% &ron!hie!ta$i$ re$ult. Situ$ in:er$u$ "ay al$o &e /re$ent.

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1Choi!e 2 Ma!roor!hi%i$" 1lar.e te$te$2 ty/i!ally %e:elo/$ in /u&ertal "ale$ 0ith #ra.ile ? $yn%ro"e5 the $e!on% "o$t !o""on .eneti! !au$e o# "ental retar%ation. On karyoty/e analy$i$ o# !ell$ !ulture% in a #olate9%e#i!ient "e%iu"5 thi$ ?9linke% %i$or%er $ho0$ a %i$!ontinuity o# $tainin. on the lon. ar" o# the ? !hro"o$o"e. 1Choi!e C2 Ri!ket$ i$ not a$$o!iate% 0ith Do0n $yn%ro"e. 1Choi!e D2 Re% &loo% !ell $i!klin. o!!ur$ in $i!kle !ell ane"ia. The $i!kle !ell "utation i$ lo!ali7e% to in%i:i%ual 89 .lo&in .ene$ an% %oe$ not re$ult #ro" tri$o"y G1. 1Choi!e '2 Chroni! "yelo.enou$ leuke"ia 1CML2 i$ a$$o!iate% 0ith the Phila%el/hia !hro"o$o"e re!i/ro!al tran$lo!ation &et0een the lon. ar"$ o# !hro"o$o"e$ J an% GG. Thi$ tran$lo!ation #u$e$ the CR .ene o# !hro"o$o"e GG to the A L .ene o# !hro"o$o"e J. Aaryoty/e analy$i$ "i.ht $ho0 elon.ation o# the lon. ar" o# one !hro"o$o"e J. E%u!ational O&<e!ti:e= Tri$o"y G1 1>35 ??5 MG12 i$ %ete!ta&le &y !yto.eneti! karyoty/e analy$i$ an% i$ the "o$t !o""on !au$e o# !on.enital "ental retar%ation. Patient$ 0ith Do0n $yn%ro"e are G,9>, ti"e$ "ore likely to %e:elo/ ALL than the .eneral /o/ulation.

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Q NO 44: A 1>9year9ol% "ale e)/erien!e$ $e:ere /rolon.e% &lee%in. a#ter ha:in. a tooth e)tra!te%. ;e al$o ha$ a hi$tory o# "ulti/le e/i$o%e$ o# /ain#ul <oint $0ellin. #ollo0in. "inor trau"a. E:aluation re:eal$ that he ha$ an inherite% %i$or%er. No0 hi$ ol%er $i$ter 0ho %oe$ not ha:e thi$ !on%ition5 a$k$ a&out the ri$k that her o0n !hil%ren 0ill &e a##e!te%. The &e$t /ro&a&le e$ti"ate i$= A. Near , . 1FG C. 1F> D. 1FE. 1F1E '. 1FHG Explanation: The "ale /atient %e$!ri&e% a&o:e ha$ a hi$tory o# e)!e$$i:e &lee%in. an% he"arthro$e$5 $u..e$tin. a %ia.no$i$ o# he"o/hilia A or 5 &oth ?9linke% re!e$$i:e !oa.ulation #a!tor %e#i!ien!ie$. The /ro&a&ility that hi$ $i$ter 0ill .i:e &irth to an a##e!te% !hil% !an &e !al!ulate% a$ #ollo0$= W Pro&a&ility 1/12 that $i$ter i$ a !arrier L ,.+ W PG that $i$ter 0ill ha:e a "ale !hil% L ,.+ W PH that o##$/rin. o# #e"ale !arrier 0ill inherit the ? !hro"o$o"e 0ith the he"o/hilia .ene L ,.+ The /ro&a&ility that the $i$ter 0ill ha:e an a##e!te% $on i$ thu$ the /ro&a&ility that all three o# the a&o:e e:ent$ take /la!e. i.e. the /ro%u!t o# their in%i:i%ual /ro&a&ilitie$5 /1 ) /G ) /H L 1FG ) 1FG ) 1FG L 1Fe. E%u!ational O&<e!ti:e= The /ro&a&ility that a #e"ale $i&lin. o# a "ale a##e!te% &y an ?9linke% re!e$$i:e %i$ea$e 0ill .i:e &irth to an a##e!te% !hil% i$ 1F e.

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Q NO 45: A 1E9year9ol% Cau!a$ian #e"ale /re$ent$ to your o##i!e 0ith a"enorrhea. She ha$ ne:er ha% "en$e$. She i$ 13+ !" tall5 0ei.h$ E+ k. 11>H l&2 an% ha$ #ully %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$. Pel:i! e)a"ination re:eal$ a $hortene% :a.inal !anal 0ith a ru%i"entary uteru$. Whi!h o# the #ollo0in. i$ the "o$t likely %ia.no$i$ in thi$ /atientK A. Aline#elter $yn%ro"e . Turner $yn%ro"e C. G19hy%ro)6la$e %e#i!ien!y D. >3 ??? karyoty/e E. Mar#an $yn%ro"e '. Mullerian a.ene$i$ G. Aall"ann $yn%ro"e Explanation: In the $e)ually un%i##erentiate% e"&ryo 1UE 0eek$ o# .e$tation21 t0o /air$ o# .enital %u!t$ are /re$ent= the /ara"e$one/hri! 1Mullerian2 %u!t$ an% the "e$one/hri! 1Wol##ian2 %u!t$. In the #e"ale #etu$5 the Mullerian %u!t$ .i:e ri$e to #allo/ian tu&e$5 uteru$1 !er:i)5 an% u//er :a.ina5 0hile the Wol##ian %u!t$ %e.enerate #ro" the la!k o# hor"onal $ti"ulation. A&nor"al tran$#or"ation o# the Mullerian %u!t$ into the #e"ale .enitalia re$ult$ in a 0i%e ran.e o# %e#e!t$ that in!lu%e 1&ut are not li"ite% to2 the #ollo0in.= hy/o/la$ia or a.ene$i$ o# the :a.ina an% uteru$N %u/li!ation o# the :a.ina1 !er:i) an% uteru$N an% uni!ornuate5 &i!ornuate an% $e/tate uteru$. e!au$e the /atient /re$ente% here ha$ #ully %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$5 nor"al le:el$ o# e$tro.en$ an% .ona%otro/in$ are to &e e)/e!te%. When "en$e$ are a&$ent in the !onte)t o# nor"ally #un!tionin. o:arie$ an% a nor"ally #un!tionin. anterior /ituitary .lan%5 the !on%ition i$ !on$i%ere% to &e eu.ona%otro/i! a"enorrhea. The t0o "o$t !o""on !au$e$ o# /ri"ary eu.ona%otro/i! a"enorrhea are i"/er#orate hy"en or Mullerian %u!t ano"alie$. The latter !on%ition i$ the "ore likely !au$e o# thi$ /atient($ uterine hy/o/la$ia. 1Choi!e A2 Aline#elter $yn%ro"e 1karyoty/e >3 ??@2 a##e!t$ "ale$ an% i$ !hara!teri7e% &y tall $tature5 /oorly %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$5 atro/hi! te$te$ an% in#ertility. 1Choi!e 2 Turner $yn%ro"e 1karyoty/e >+?O2 i$ a !o""on !au$e o# /ri"ary a"enorrhea. A##e!te% in%i:i%ual$ ha:e $hort $tature5 0e&&e% ne!k5 $hiel%e% !he$t an% B$treake%C 1#i&roti!2 o:arie$. They %o not %e:elo/ $e!on%ary $e)ual !hara!teri$ti!$. 1Choi!e C2 G19hy%ro)yla$e %e#i!ien!y :arie$ in $e:erity an% "ay "ani#e$t in neonate$ or later in li#e 1e:en in youn. a%ult$2. A%ult9on$et G19hy%ro)yla$e %e#i!ien!y "ay /re$ent a$ a"enorrhea5 hir$uti$" an% :irili7ation. ;y/onatre"ia an% hy/erkale"ia are !hara!teri$ti! #in%in.$. 1Choi!e D2 The >3 ??? karyoty/e i$ not a$$o!iate% 0ith a"enorrhea5 thou.h $o"e a##e!te% in%i:i%ual$ "ay ha:e $li.htly %e!rea$e% 1, $!ore$. 1Choi!e E2 Mar#an $yn%ro"e i$ not a$$o!iate% 0ith a"enorrhea. 1Choi!e G2 Aall"ann $yn%ro"e o!!ur$ %ue to %i"ini$he% $ynthe$i$ o# .ona%otro/i! hor"one$ &y the anterior /ituitary .lan%. The !on%ition /re$ent$ 0ith /ri"ary a"enorrhea5 a&$ent $e!on%ary $e)ual !hara!teri$ti!$5 an% an ol#a!tory $en$ory %e#e!t.

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E%u!ational O&<e!ti:e= Pri"ary a"enorrhea in a /atient 0ith #ully %e:elo/e% $e!on%ary $e)ual !hara!teri$ti!$ $u..e$t$ the /re$en!e o# an anato"i! %e#e!t in the .enital tra!t5 $u!h a$ i"/er#orate hy"en or MXllerian %u!t a&nor"alitie$.

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Q NO 46: A GH9year9ol% Cau!a$ian "ale 0ith "il% "ental retar%ation ha$ lar.e ear$5 a lon. #a!e5 a /ro"inent "an%i&le5 an% lar.e te$te$. ;i$ han% <oint$ are hy/ere)ten$i&le on /hy$i!al e)a"ination. Whi!h o# the #ollo0in. i$ the "o$t likely %ia.no$i$ in thi$ /atientK Aline#elter $yn%ro"e . Turner $yn%ro"e C. >3 ?@@ karyoty/e D. >3 ??? karyoty/e E. Te$ti!ular #e"ini7ation $yn%ro"e '. MXllerian a.ene$i$ G. Mar#an $yn%ro"e ;. 'ra.ile ? $yn%ro"e

A.

Explanation: Thi$ /atient %i$/lay$ the !lini!al #eature$ o# #ra.ile ? $yn%ro"e5 0hi!h i$ the "o$t !o""on !au$e o# inherite% "ental retar%ation an% the $e!on% lea%in. o:erall !au$e o# !on.enital "ental retar%ation a#ter Do0n $yn%ro"e. A "ale that inherit$ one a&nor"al ? !hro"o$o"e 0ill al0ay$ %e:elo/ the %i$ea$e5 a$ he ha$ only one ? !hro"o$o"e. A #e"ale 0ith one a&nor"al ? !hro"o$o"e .enerally ha$ a "il%er !lini!al /re$entation an% "ore nor"al !o.niti:e %e:elo/"ent &e!au$e $he inherit$ t0o ? !hro"o$o"e$5 0ith one o# the t0o ran%o"ly ina!ti:ate% in e:ery !ell. O:erall the /ro.no$i$ o# #e"ale$ 0ith #ra.ile ? i$ hi.hly :aria&le an% !annot &e a!!urately /re%i!te%. Male$ 0ith #ra.ile ? $yn%ro"e ty/i!ally %e"on$trate$ $e:eral o# the #ollo0in. $i.n$= 1. Mil%9to9"o%erate "ental retar%ation 11, o# >,9-+25 $/ee!h an% lan.ua.e %elay5 auti$ti! &eha:ior an% AD;D G. Lon. #a!e5 /ro"inent <a0$1 lar.e ear$5 an% !le#t /alate H. Ma!roor!hi%i$" >. Mitral :al:e /rola/$e +. Short hei.ht5 <oint la)ity5 $!olio$i$5 /e$ !a:u$5 %ou&le9<ointe% thu"&$5 an% a $in.le /al"ar !rea$e 1Choi!e A2 Aline#elter $yn%ro"e 1>12,1@2 "ay &e a$$o!iate% 0ith "il% "ental retar%ation or nor"al intelli.en!e. The ty/i!al /atient i$ a tall "ale 0ith .yne!o"a$tia5 $"all te$te$5 an% in#ertility. 1Choi!e 2 'e"ale$ 0ith Turner $yn%ro"e 1>+?O2 /re$ent 0ith /ri"ary a"enorrhea an% "il% "ental retar%ation5 thou.h nor"al !o.niti:e #un!tion i$ al$o /o$$i&le. The ty/i!al /atient ha$ $hort $tature5 0e&&e% ne!k5 $hiel%e% !he$t an% o:arian %y$.ene$i$. 1Choi!e C2 The >3?@@ karyoty/e i$ !hara!teri7e% &y tall $tature5 $e:ere a!ne5 an% "il% %elay$ in &oth "otor an% lan.ua.e %e:elo/"ent. Early re$ear!h $u..e$te% that the$e in%i:i%ual$ 0ere /rone to hei.htene% a..re$$ion a$ 0ell5 &ut "ore re!ent $tu%ie$ $u..e$t the in!rea$e in !ri"inal a!ti:ity a"on. the >1 ?@@ /o/ulation$ i$ a!tually $e!on%ary to lo0er "ean IQ$ an% a$$o!iate% /oor <u%."ent. 1Choi!e D2 The >3??? karyoty/e i$ ty/i!ally !lini!ally $ilent. So"e a##e!te% in%i:i%ual$ "ay ha:e $li.htly %e!rea$e% IQ $!ore$. 1Choi!e E2 Te$ti!ular #e"ini7ation $yn%ro"e 1!o"/lete an%ro.en in$en$iti:ity2 i$ !hara!teri7e% &y nor"al e)ternal #e"ale .enitalia &ut entirely a&$ent 0ol##ian an% "ullerian $tru!ture$. Mental retar%ation5 #a!ial %e#or"itie$5 an% "a!roor!hi%i$" are not $een. 1Choi!e '2 MXllerian a.ene$i$ re$ult$ in the !on.enital a&$en!e o# the :a.ina an% :aria&le uterine %e:elo/"ent. Mental retar%ation5 #a!ial %e#or"itie$5 an% "a!roor!hi%i$" are not $een.

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1Choi!e G2 Mar#an $yn%ro"e i$ !hara!teri7e% &y tall $tature5 ara!hno%a!tyly 1lon. an% thin #in.er$25 e!to/ia lenti$ 1len$ %i$/la!e"ent25 an% %ilatation o# the /ro)i"al aorta. Mental retar%ation #a!ial %e#or"itie$ an% "a!roor!hi%i$" are not $een. E%u!ational O&<e!ti:e= 'ra.ile ? $yn%ro"e ari$e$ $e!on%ary to an in!rea$e in the nu"&er o# trinu!leoti%e re/eat$ 0ithin the 'MR1 .ene on the ? !hro"o$o"e. Ty/i!al !lini!al #eature$ o# thi$ !on%ition in!lu%e "ental retar%ation1 #a!ial %e#or"itie$5 an% "a!roor!hi%i$".

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Q NO 47: A 1G9year9ol% Cau!a$ian "ale 0ith hi$tory o# $ei7ure %i$or%er e)/erien!e$ $e:eral $troke9like e/i$o%e$ 0ith re$i%ual neurolo.i!al %e#i!it. ;e al$o $u##er$ #ro" "u$!le 0eakne$$. loo% te$t$ $ho0 in!rea$e% $eru" la!tate le:el$ &oth /o$t9 e)er!i$e an% at re$t. Thi$ /atient($ !on%ition in kno0n to &e "aternally inherite%. Thi$ /atient($ $i$ter i$ al$o a##e!te% &y the $a"e %i$or%er5 &ut $he %i$/lay$ :ery #e0 $y"/to"$. Whi!h o# the #ollo0in. i$ the "o$t likely e)/lanation #or the :aria&ility in !lini!al /re$entation &et0een the /atient an% hi$ $i$terK A. Geneti! i"/rintin. . ;etero/la$"y C. Anti!i/ation D. Lo0 e)/re$$ion :aria&ility E. 'e"ale $/arin. Explanation: Mito!hon%ria ha:e a $"all a"ount o# their o0n DNA5 !alle% "ito!hon%rial DNA 1"tDNA25 0hi!h !an ha:e %eletion$ an% /oint "utation$ <u$t like re.ular DNA. Mito!hon%rial %i$or%er$ 1"utation$ in "tDNA2 are uni6ue in that they are e)!lu$i:ely inherite% #ro" one($ "other. Re!all that the o:u" i$ relati:ely lar.e an% ha$ "any !o/ie$ o# "tDNAN 0herea$5 the #e0 !o/ie$ o# "tDNA /re$ent in $/er" are lo$t %urin. #ertili7ation. Mito!hon%rial %i$ea$e$ a##e!t &oth "ale an% #e"ale o##$/rin. 0ith e6ual #re6uen!y 11,,425 &ut there are :aria&le %e.ree$ o# $e:erity. Thi$ :aria&ility o!!ur$ &e!au$e5 %urin. "ito$i$5 "ito!hon%ria are ran%o"ly %i$tri&ute% &et0een %au.hter !ell$. A$ a re$ult5 $o"e !ell$ !ontain "ito!hon%ria 0ith "o$tly %a"a.e% "tDNA5 0hile $o"e !ontain "o$tly nor"al "ito!hon%rial .eno"e$. Thi$ "i)ture o# t0o ty/e$ o# .eneti! "aterial i$ !alle% ;etero/la$"y an% i$ re$/on$i&le #or the !lini!al :aria&ility o# "ito!hon%rial %i$ea$e$. The #ollo0in. "ito!hon%rial $yn%ro"e$ are i"/ortant= 1. Le&er here%itary o/ti! neuro/athy lea%$ to &ilateral :i$ion lo$$. G. Myo!loni! e/ile/$y 0ith ra..e%9re% #i&er$= "yo!loni! $ei7ure$ an% "yo/athy a$$o!iate% 0ith e)er!i$e. Skeletal "u$!le &io/$y $ho0$ irre.ularly $ha/e% "u$!le #i&er$ 1ra..e% re% #i&er$2. H. Mito!hon%rial en!e/halo"yo/athy 0ith la!ti! a!i%o$i$ en% $troke9like e/i$o%e$ 1MELAS2. The !lini!al /re$entation o# MELAS i$ %e$!ri&e% in thi$ :i.nette. 1Choi!e A2 Geneti! i"/rintin. i$ a $ele!ti:e ina!ti:ation o# /aternal or "aternal allele$. Thi$ /heno"enon e)/lain$ the %i##eren!e$ in !lini!al /re$entation &et0een Pra%er9Willi an% An.el"an $yn%ro"e$. 1Choi!e C2 Anti!i/ation re#er$ to the in!rea$e in $e:erity o# .eneti! %i$or%er$ in $u&$e6uent .eneration$. Anti!i/ation i$ o#ten $een %i$ea$e$ in:ol:in. an in!rea$e% nu"&er o# trinu!leoti%e re/eat$5 $u!h a$ ;untin.ton %i$ea$e an% 'ra.ile ? $yn%ro"e. 1Choi!e D2 Daria&le e)/re$$i:ity re#er$ to the %i##eren!e$ in $e:erity o# auto$o"al %o"inant %i$or%er$. 'or e)a"/le5 a /atient 0ith Mar#an $yn%ro"e "ay ha:e only tall $tature5 0hile another /atient 0ith the $a"e .eneti! %e#e!t 0ill ha:e tall $tature5 aorti! root %ilation5 an% len$ %i$lo!ation. Daria&le e)/re$$i:ity i$ not a #eature o# "ito!hon%rial %i$ea$e$. 1Choi!e E2 'e"ale $/arin. i$ not !hara!teri$ti! o# "ito!hon%rial %i$or%er$. oth "ale$ an% #e"ale$ are e6ually a##e!te% in "ito!hon%rial %i$or%er$. E%u!ational O&<e!ti:e= Mito!hon%rial %i$ea$e$ are !hara!teri7e% &y e)!lu$i:ely9 "aternal inheritan!e. The :aria&le $e:erity o# the$e %i$ea$e$ i$ e)/laine% &y the ran%o" %i$tri&ution o# nor"al an% "utate% "ito!hon%ria &et0een %au.hter !ell$ %urin. "ito$i$N a$ a re$ult5 $o"e !ell$ "ay ha:e !o"/letely healthy "ito!hon%ria5 0hile other !ell$ !ontain "ito!hon%ria a##e!te% &y .eneti! "utation 1;etero/la$"y2. MELAS i$ a "ito!hon%rial $yn%ro"e.

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Q NO 48: When intro%u!e% in%i:i%ually1 t0o %i##erent "utant $train$ o# a%eno:iru$ %o not !au$e !yto/athi! e##e!t$ in a hu"an !ell !ulture. ut 0hen the !ulture% !ell$ are $i"ultaneou$ly e)/o$e% to &oth "utant $train$5 a ne0 :iral /ro.eny $train i$ /ro%u!e% that !au$e$ !ellular enlar.e"ent an% a..re.ation. Whi!h o# the #ollo0in. "o$t likely !ontri&ute% to the #or"ation o# the /ro.eny :iral $trainK A. Rea$$ort"ent . Re!o"&ination C. Tran$#or"ation D. Phenoty/i! "i)in. E. Inter#eren!e Explanation: Thi$ $!enario %e$!ri&e$ the e)!han.e o# .eneti! in#or"ation &et0een t0o :iru$ $train$ that ha:e non9#ra."ente%5 %ou&le9$tran%e% DNA .eno"e$. Su!h an e)!han.e a"ount$ to re!o"&ination5 0hi!h "ay &e %e#ine% a$ the e)!han.e o# .ene$ &et0een t0o !hro"o$o"e$ :ia !ro$$in. o:er 0ithin ho"olo.ou$ re.ion$. The re$ultin. /ro.eny 0ill ha:e trait$ not /re$ent $i"ultaneou$ly in either /arent :iru$. 1Choi!e A2 Rea$$ort"ent re#er$ to !han.e$ in .eno"i! !o"/o$ition that o!!ur 0hen ho$t !ell$ are !o9in#e!te% 0ith t0o $e."ente% :iru$e$ that e)!han.e 0hole .eno"e $e."ent$. Thi$ /ro!e$$ !an !au$e $u%%en alteration$ in the $ur#a!e anti.en$ o# the :iral /ro.eny5 a$ o&$er:e% 0ith the hi.hly "uta.eni! in#luen7a :iru$. e!au$e the a%eno:iru$ .eno"e !ontain$ non9$e."ente%5 %ou&le9$tran%e% DNA5 it %oe$ not en.a.e in rea$$ort"ent. 1Choi!e C2 Tran$#or"ation i$ .enerally %e#ine% a$ the u/take o# nake% DNA &y a /rokaryoti! or eukaryoti! !ell. In :irolo.y thi$ ter" "ay al$o &e u$e% to %e$!ri&e the in!or/oration o# :iral DNA into a ho$t !ell !hro"o$o"e. Tran$#or"ation alter$ the .eneti! !o"/o$ition o# the ho$t !ell &ut ty/i!ally !au$e$ no .eno"i! !han.e in /ro.eny :irion$. 1Choi!e D2 Phenoty/i! "i)in. re#er$ to !o9in#e!tion o# a ho$t !ell &y t0o :iral $train$5 re$ultin. in /ro.eny :irion that !ontain$ nu!leo!a/$i% /rotein$ #ro" one $train an% the .eno"e o# the other $train. In thi$ !a$e5 $in!e neither :irion $train 0a$ !yto/athi! 1e:en thou.h &oth $train$ !oul% a//arently in$ert their .eno"e$ into the ho$t !ell line2. Rearran.e"ent o# the !a/$i% /rotein$ aroun% either un!han.e% .eno"e 0oul% not &e e)/e!te% to !on#er ne0 !yto/athi! :irulen!e to the /ro.eny :irion$. 1Choi!e E2 Inter#eren!e i$ the inhi&ition &y one :iru$ o# the re/li!ation an%For relea$e o# a $e!on% :iru$ that i$ in#e!tin. the $a"e !ell. Si"/le inter#eren!e 0oul% not re$ult in re!o"&inant /ro.eny :irion$. E%u!ational O&<e!ti:e= Geno"e re!o"&ination &et0een t0o %e#e!ti:e :iru$e$ !o9in#e!tin. the $a"e ho$t !ell !an yiel% a !yto/athi! 0il%9ty/e .eno"e. Re!o"&ination i$ .ene e)!han.e that o!!ur$ throu.h the !ro$$in. o:er o# t0o %ou&le9$tran%e% DNA "ole!ule$. Rea$$ort"ent %e$!ri&e$ the "i)in. o# .eno"e $e."ent$ in t0o or "ore $e."ente% :iru$e$ that in#e!t the $a"e ho$t !ell.

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Q NO 49: An in#ant &orn to a HE9year9ol% Cau!a$ian #e"ale %e"on$trate$ $o"e %y$"or/hi! #a!ial #eature$ an% a holo$y$toli! "ur"ur at the le#t $ternal &or%er. Aaryoty/e analy$i$ i$ !on$i$tent 0ith tri$o"y G1. Whi!h o# the #ollo0in. a%%itional #in%in.$ 0oul% &e "o$t e)/e!te% in thi$ in#antK A. Cle#t /alate . Poly%a!tyly C. Sin.le /al"ar !rea$e D. Ro!ker9&otto" #eet E. Ma!ro!e/haly '. Ma!roor!hi%i$" Explanation: Do0n $yn%ro"e i$ the "o$t !o""on auto$o"al tri$o"y i%enti#ie% in li:e&orn in#ant$. A$ "any a$ J+4 o# Do0n $yn%ro"e !a$e$ ari$e %ue to !hro"o$o"al non%i$<un!tion %urin. "aternal "eio$i$ 1>3 ??5 MG12 an a&nor"ality that /o$iti:ely !orrelate$ 0ith in!rea$in. "aternal a.e. T0o o# the "ore /ro"inent an% !on$i$tent le!ture$ o# Do0n $yn%ro"e are "ental retar%ation an% #a!ial %y$"or/hi$". Al"o$t e:ery or.an an% $y$te"5 ho0e:er5 i$ a##e!te%. The !hara!teri$ti! Do0n $yn%ro"e a&nor"alitie$ are !ate.ori7e% &y $y$te" &elo0.

1Choi!e A2 Cle#t /alate i$ a$$o!iate% 0ith tri$o"y 1H 1Patau $yn%ro"e2. 1Choi!e 2 Poly%a!tyli$" a$$o!iate% 0ith tri$o"y 1H 1Patau $yn%ro"e2. 1Choi!e D2 Ro!ker9&otto" #eet are a$$o!iate% 0ith &oth tri$o"y 1H 1Patau $yn%ro"e2 an% tri$o"y 1- 1E%0ar%$ $yn%ro"e2. 1Choi!e E2 Ma!ro!e/haly i$ not a ty/i!al !lini!al #eature o# the "ore !o""on !hro"o$o"al $yn%ro"e$. 1Choi!e '2 Ma!roor!hi%i$" i$ a$$o!iate% 0ith #ra.ile ? $yn%ro"e. A##e!te% in%i:i%ual$ al$o ha:e tall $tature5 lar.e ear$5 lon. #a!e5 an% "ental retar%ation. E%u!ational O&<e!ti:e= Tri$o"y G1 1Do0n $yn%ro"e2 i$ !hara!teri7e% &y "ental retar%ation5 #a!ial %y$"or/hi$"5 $in.le /al"ar !rea$e5 en%o!ar%ial !u$hion %e#e!t$5 an% %uo%enal atre$ia. A##e!te% in%i:i%ual$ ha:e an in!rea$e% ri$k o# AML9M3 an% ALL in !hil%hoo% an% early Al7hei"er %i$ea$e in a%ulthoo%.

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Q NO 50: A G+9year9ol% Cau!a$ian "ale ha$ a $e:ere intoleran!e to !ertain "e%i!ation$. On t0o o!!a$ion$5 hi$ rea!tion$ to :ariou$ "e%i!ation$ ha:e ne!e$$itate% ho$/ital a%"i$$ion. ;i$ #a"ily /e%i.ree 0ith re$/e!t to thi$ !on%ition i$ $ho0n &elo0.

Thi$ !on%ition #ollo0$ 0hi!h inheritan!e /atternK A. Auto$o"al %o"inant . Auto$o"al re!e$$i:e C. ?9linke% %o"inant D. ?9linke% re!e$$i:e E. Mito!hon%rial Explanation: Thi$ /e%i.ree $ho0$ that only "ale$ are a##e!te% &y thi$ %ru. intoleran!e. S/e!i#i!ally5 "ale o##$/rin. o# una##e!te% /arent$ are a##e!te%. There i$ no e:i%en!e o# "ale9to9"ale tran$"i$$ion. Thi$ /attern i$ "o$t !on$i$tent 0ith ? linke% re!e$$i:e inheritan!e #ro" a$y"/to"ati! hetero7y.ou$ 1!arrier2 #e"ale$. GEPD %e#i!ien!y5 0hi!h !au$e$ an a!ute he"olyti! ane"ia in rea!tion to o)i%ant %ru.$5 #ollo0$ an ?9 linke% re!e$$i:e /attern o# inheritan!e. Auto$o"al %o"inant inheritan!e re6uire$ that at lea$t one /arent o# the a##e!te% in%i:i%ual e)/re$$ the trait a$ 0ell. In auto$o"al re!e$$i:e inheritan!e. G+4 o# o##$/rin. o# una##e!te% 1hetero7y.ou$ !arrier2 /arent$ 0ill &ear the trait. In ? linke% %o"inant inheritan!e5 at lea$t one /arent 1o# either $e)2 i$ a##e!te% an% all #e"ale o##$/rin. o# a##e!te% "ale$ ha:e the %i$ea$e. 'inally5 !on%ition$ 0ith "ito!hon%rial inheritan!e are tran$"itte% only &y the "other5 an% all o##$/rin. o# a##e!te% #e"ale$ are likely to $ho0 $i.n$ o# %i$ea$e. E%u!ational O&<e!ti:e= In ?9linke% re!e$$i:e inheritan!e5 "ale !hil%ren o# una##e!te% /arent$ !ontra!t the %i$ea$e. There i$ no "ale9to9"ale tran$"i$$ion. GEPD %e#i!ien!y5 0hi!h !au$e$ an a!ute he"olyti! ane"ia in rea!tion to o)i%ant %ru.$5 #ollo0$ thi$ /attern.

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