A child with prader-Willi syndrome is identified by DNA methylation analysis showing absence of paternal 15q11-q13 expression. Which of the following is the mechanism in approximately 25% of cases?
- A Paternal deletion 15q11-q13 (70%)
- B Point mutation in SNRPN gene
- C Maternal uniparental disomy (UPD) of chromosome 15 ✓
- D Imprinting centre defect
Explanation
Prader-Willi syndrome results from lack of expression of paternally imprinted genes at 15q11-q13. Approximately 70% of cases are due to paternal deletion of 15q11-q13; approximately 25% are due to maternal uniparental disomy (mUPD) — the child inherits both copies of chromosome 15 from the mother, resulting in no paternal contribution at this region; ~2–5% are due to imprinting centre defects. DNA methylation analysis identifies the syndrome regardless of mechanism. Angelman syndrome, in contrast, lacks maternal expression at the same locus. The SNRPN gene is used as a methylation marker but point mutations are extremely rare in PWS.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.