Question

Which of the following is true about Fragile X syndrome?

• A. Triple nucleotide CAG sequence mutation
• B. 10% female carriers are mentally retarded
• C. Males have IQ 20-40
• D. Gain of function mutation

Hint:

It is a CGG repeat loss-of-function disorder; fully affected males have IQ around 40.

Answer 1

The Correct Option is C

Step 1: Fragile X syndrome arises from a fragile site on the X chromosome (Xq27.3) due to expansion of a CGG trinucleotide repeat in the FMR1 gene. It is the commonest inherited cause of intellectual disability in males.
Step 2: When the repeat fully expands, the FMR1 gene is silenced, so there is a loss of function (no FMRP protein), not a gain of function. This rules out option (d).
Step 3: The repeat is CGG, not CAG, so option (a) is wrong (CAG expansions cause Huntington disease and several spinocerebellar ataxias).
Step 4: Affected males with complete FMR1 silencing have severe intellectual disability with an average IQ of about 40 (range roughly 20-40). This matches option (c). The carrier-female figure in option (b) is not the standard 10 percent (about 20 percent of premutation carrier women develop primary ovarian insufficiency, and only a proportion of full-mutation carrier females are affected), so (c) is the best answer.