A 4-year-old boy has global developmental delay, macrocephaly, large ears, a long face with prominent jaw, and autism spectrum behaviour. His mother's brother had similar features with intellectual disability. DNA testing would most likely show which abnormality?

• A Point mutation in the MECP2 gene
• B Deletion of the long arm of chromosome 15 inherited paternally
• C Expansion of CGG trinucleotide repeats beyond 200 copies in the FMR1 gene ✓
• D Expansion of CAG repeats in the HTT gene

Explanation

Fragile X syndrome results from full methylation-silencing expansion of CGG repeats (>200) in the 5' untranslated region of FMR1 on Xq27.3, causing loss of FMRP protein. Inheritance is X-linked dominant with anticipation through maternal transmission, explaining the affected maternal uncle. Paternal 15q deletion gives Prader-Willi, MECP2 mutation causes Rett syndrome in girls, and CAG expansion in HTT causes Huntington disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.