FRAGILE X SYNDROME

1 ETIOLOGY
X-Linked Dominant disorder
Deficiency in FMRP (Fragile X Mental Retardation Protein)
Encoded by FMR1 gene on X chromosome
FMR1 gene is needed for neurodevelopment
FMR1 gene is affected by a trinucleotide expansion in noncoding 5UTR
Mutated FMR1 gene CGG tandem repeats in noncoding 5 UTR

2 PATHOGENESIS
The FMR1 gene mutation is a quantity problem with not enough FMRP
Fragile X syndrome also shows anticipation
Male Penetrance = 100%
Mental retardation; large ears; prominent jaw; macro-orchidism
Female Penetrance = 60%
Mental retardation