A 5-year-old boy has a history of paternal grandmaternal intellectual disability. He has macro-orchidism, prominent ears, large jaw, and an IQ of 55. His mother is phenotypically normal but a carrier. The responsible mutation is best described as:

• A Deletion of chromosome 15q11-q13 of paternal origin
• B CAG repeat expansion in the huntingtin gene
• C Point mutation in the FGFR2 gene
• D Trinucleotide CGG repeat expansion in the FMR1 gene ✓

Explanation

Fragile X syndrome is caused by expansion of the CGG trinucleotide repeat in the 5' UTR of the FMR1 gene on the X chromosome. Normal alleles have <55 repeats; premutation carriers (55–200 repeats) are phenotypically normal or mildly affected; full mutation (>200 repeats) causes methylation and silencing of FMR1, leading to intellectual disability, macro-orchidism, prominent ears, and prognathism. It follows X-linked inheritance with anticipation (repeat expansion can occur in future generations). The family history pattern with an apparently normal carrier mother is characteristic.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.