An 8-year-old boy has severe obesity with hyperphagia, short stature, small hands and feet, almond-shaped eyes, and undescended testes. Methylation analysis shows loss of expression of paternally inherited genes at 15q11-q13. What is the underlying mechanism?

• A Deletion of the maternally derived UBE3A gene
• B Uniparental disomy of chromosome 15 from the father
• C Loss of the paternal contribution to 15q11-q13 ✓
• D Expansion of GAA repeats in the SNRPN gene

Explanation

Prader-Willi syndrome arises when paternally expressed genes in 15q11-q13 are lost, by paternal deletion (about 70 percent), maternal uniparental disomy, or an imprinting defect. Angelman syndrome is the mirror image, caused by loss of the maternally expressed UBE3A. Paternal uniparental disomy of 15 would duplicate paternal genes and cannot cause Prader-Willi, and there is no repeat expansion in this region.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.