Disease Clinical features Gene and Gene Key Pathogenesis Genetic Features Molecular

product mutations of the Diagnostic Test

mutation
Cystic  Pulmonary Cystic Fibrosis 1,400 Epithelial cells ALLELIC Genetic
Fibrosis disease Transmembrane mutations lining the HETEROGENEITY heterogeneity
 Meconium ileus Conductance of CFTR sweat duct 1:2500 incidence means that
in 10-20% of Regulator (CFTR) F508del Cl- and Na+ are 1:25 carrier there is no easy
newborns Member of ATP (∆F508) unable to go frequency or sensitive
 Pancreatic binding cassette found in inside the molecular test
insuffiency subfamily C 70% of cell..↑sweat for CF
 Male infertility CFTR mRNA mutated Cl- conc. Screening for 25
encodes 1480 CFTR Epithelial cells common
amino acid alleles lining the mutations has
protein with Class II airway Cl- is ↑sensitivity of
three functions: Defective unable to get 90% in
Cl ion channel Processing out of the cell, Caucasians and
Regulates Na+ and H20 50% in African-
opening and follow into the Americans
closing of ion cell, Reproductive
pore dehydrated partner of
Regulates activity mucus person with CF
of other ion relative with CF
channels or known carrier
GATE AND GATE Caucasian and
KEPPER Jewish persons
who are
pregnant or
planning
pregnancy
Also available to
other ethnic
groups
Symptomatic
individuals-
confirm dx.
Determine
familial
mutations
Prenatal dx if
both partners
are carriers
children with
severe asthma
and other
CPulCond
 Disease Clinical Gene and Gene Key Pathogenesis Genetic Molecular
features product mutations of the Features Diagnostic Test
mutation
Hereditary High absorption Hemochromatosis Major w/o functional AUTOSOMAL Molecular genetic
Hemochromatosis of iron in the GI (HFE) mutant HFE, iron RECESSIVE AND testing of HFE
tractexcessive allele C282Y uptake INCOMPLETE gene, Cys282Tyr
storage of iron Cys282Tyr through the PENETRANCE and His63Asp
(liver, skin, and Tf/TfR system 1:200-1:400 mutations about
pancreas, heart, His63Asp in intestinal incidence 87% of individuals
joints, testes) crypt is carrier frequency with HHC are
Symptoms impaired. 1:10 Caucasians of either
develop btwn These cells fail Northern homozygous for
40-60 yrs in to sense European ancestry the C282Y
males and after circulating Tf- mutation or
menopause for bound iron compound
females hepatic levels heterozygotes for
fibrosis or leads to the C282Y/H63D
cirrhosis is ↑level of mutations
common in expression of
untreated other iron
persons after transporters
age 40 ↑ levels of
expression of
other iron
transporters
Only 2/3 males
serrum and 1/2 of
transferritin-iron females
saturation levels homozygous for
>62% C282Y mutation
evaluated for show ↑
HHC transferring
serum ferritin saturation and/or
levels >300 ↑ serum ferritin
ng/ml in men levels penetrance
>200 ng/ml differs among
women populations
population-wide
primary genetic
screening for HHC
will identify large
numbers of “non-
expressors” who
carry HFE
mutations but do
not demonstrate
 iron overload

Disease Clinical Gene and Gene Key mutations Pathogen Genetic Molecular
features product esis of the Features Diagnostic
mutation Test
Factor V Leiden Hereditary Factor V Leiden Point mutation in SINGLE
Thrombophilia deficiency in allele-single point the Coagulation MUTANT
proteins mutation in Factor V Factor V (F5) ALLELE
associated gene at nucleotide gene associated RESPONSIBLE
with Arginine (Arg) with with increased FOR MOST
coagulation Glutamine (Gln) at risk of CASES
predispose to aa residue 506. One thromboembolis AUTOSOMAL
↑ risk for of 3 APC cleavage m via APC DOMINANT
thrombosis sites in the Factor V resistance but
protein Activated protein homozygotes
resistance at ↑ risk for
developing
DVT vs.
heterozygotes
for this mutant
allele
INCOMPLETE
DOMINANCE
G1691A (R506Q)
mutation results in
10-fold slower
Factor V inactivation
by Activated Protein
C (APC resistance)