A child presents with angelman syndrome — characterized by seizures, severe intellectual disability, inappropriate laughter, and absent speech. The genetic mechanism responsible in most cases is:

• A Paternal deletion of 15q11-q13, silencing imprinted UBE3A
• B Trinucleotide repeat expansion in the maternally inherited FMR1 gene
• C Maternal deletion of 15q11-q13, silencing imprinted UBE3A on the maternal chromosome ✓
• D Uniparental paternal disomy of chromosome 15

Explanation

Angelman syndrome results from loss of function of UBE3A on the maternally inherited chromosome 15q11-q13. Since UBE3A is imprinted (the paternal copy is silenced in neurons), a maternal deletion (or maternal uniparental disomy, or imprinting defect) results in no active UBE3A in neurons, causing the syndrome. Prader-Willi syndrome involves the same region but results from paternal deletion (losing paternally expressed genes like SNRPN). FMR1 expansion causes fragile X syndrome. Paternal disomy of 15 causes Prader-Willi, not Angelman.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.