Fragile X syndrome is the most common inherited cause of intellectual disability. The molecular mechanism involves:

• A Trinucleotide CGG repeat expansion in the 5' UTR of FMR1 causing gene silencing by hypermethylation ✓
• B Point mutation in the FMR1 coding sequence causing a non-functional FMRP protein
• C Deletion of the FMR1 gene on chromosome Xq27.3
• D CAG repeat expansion in FMR1 causing toxic gain-of-function protein

Explanation

Fragile X is caused by CGG trinucleotide repeat expansion (>200 repeats) in the 5' UTR of FMR1 (Xq27.3), leading to methylation of the promoter and silencing of the gene encoding FMRP (fragile X mental retardation protein). FMRP is an RNA-binding protein that regulates synaptic protein translation; its absence causes intellectual disability, macroorchidism, and dysmorphic facial features.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.