Fragile X syndrome, the most common inherited cause of intellectual disability in males, is caused by trinucleotide (CGG) repeat expansion in which gene, and the repeat number in a full mutation is:

• A FMR1 — >200 CGG repeats causing hypermethylation and silencing ✓
• B DMPK — >50 CTG repeats causing RNA splicing dysregulation
• C HTT — >36 CAG repeats causing polyglutamine aggregation
• D ATXN3 — >52 CAG repeats causing spinocerebellar ataxia

Explanation

Fragile X syndrome results from >200 CGG repeats in the 5' UTR of the FMR1 gene on Xq27.3, triggering CpG methylation of the promoter and silencing of FMR1, which encodes FMRP, a synaptic RNA-binding protein essential for dendritic mRNA translation. Normal individuals have 5-44 repeats; premutation carriers (55-200 repeats) are at risk for FXTAS (in males) and premature ovarian insufficiency (in females). DMPK CTG expansions cause myotonic dystrophy type 1. HTT CAG repeats cause Huntington disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.