1. Fragile X Syndrome (FXS) is one of the most common causes of mental retardation (MR) in humans, which shows anticipation
and exerts hypermethylation in X-xhromosome. It generally acts like an X-linked recessive inherited disease (X-LRID), but some
males do not have the disease yet they can pass it on, and some females are affected. The cause of the disease explains these
observations. Fragile X syndrome is caused by which one of the following mechanisms?
(A) a deletion of the Prader-Willi / Angelman gene on the father’s X chromosome
(B) a triplet repeat expansion
(C) chromosome breakage
(D) having two X chromosomes
19. answer: B. In Fragile X syndrome the triplet repeat expansion, CGG (located in the 5′-untranslated region of the fragile X mental retardation-1
(FMR1) gene), must reach a certain number of repeats before there is clinical manifestation of the disease. The repeat expands with succeeding
generations and eventually will reach the critical number. That is why males without the disease can pass it on to subsequent generations where it
appears because the threshold number of repeats has been reached. Females with a high number of repeats may also express some manifestations of
the disease because of skewed X inactivation.