Fragile X syndrome is the most common inherited cause of intellectual disability. The FMR1 gene mutation involves expansion of a CGG trinucleotide repeat in the 5' UTR. When repeat count exceeds which threshold does full mutation with methylation and gene silencing occur?

• A >55 repeats (premutation range)
• B >50 repeats (onset of phenotype)
• C >100 repeats (partial methylation)
• D >200 repeats (full mutation) ✓

Explanation

Normal FMR1 has 5–44 CGG repeats; 55–200 repeats define the premutation (carriers with risk of FXTAS in males and premature ovarian failure in females); >200 repeats defines full mutation, at which point the promoter becomes hypermethylated, silencing FMRP expression and causing Fragile X syndrome. FMRP is an RNA-binding protein regulating translation of synaptic proteins. The premutation range (55–200) does not typically cause intellectual disability but carries expansion risk in offspring.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.