In Prader-Willi syndrome, the molecular mechanism involves maternal uniparental disomy (UPD) of chromosome 15 or paternal deletion of 15q11-q13. The critical genes silenced are:
- A Paternally expressed genes (SNRPN, NDN, MKRN3) silenced because both copies carry maternal imprint ✓
- B Maternally expressed genes (UBE3A) silenced because both copies carry paternal imprint
- C Bi-allelic BRCA1 silencing causing DNA repair defects
- D X-linked genes silenced by lyonization
Explanation
Prader-Willi syndrome results from loss of the paternal contribution at 15q11-q13 — either by paternal deletion (most common, ~70%) or maternal UPD 15 (both chromosome 15s from mother). The paternally expressed, maternally imprinted genes in this region (SNRPN encoding SmN spliceosomal protein, NDN encoding necdin, MKRN3) are silenced by maternal imprinting on both remaining copies, producing the PWS phenotype (hypotonia, hyperphagia, obesity, hypogonadism, cognitive impairment). Angelman syndrome is the mirror: loss of maternal contribution silences UBE3A (maternally expressed). BRCA1 and X-inactivation are unrelated to imprinting disorders at 15q.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.