A child is diagnosed with Prader-Willi syndrome (PWS). Which mechanism accounts for the majority (65–70%) of PWS cases?
- A Maternal uniparental disomy of chromosome 15
- B Point mutation in the SNRPN gene
- C Paternal deletion of 15q11-q13 (loss of paternally imprinted region) ✓
- D Trisomy 15 mosaicism
Explanation
Prader-Willi syndrome results from absence of the paternal copy of chromosome 15q11-q13 (the normally active paternal alleles are lost, while maternal alleles in this region are imprinted/silenced). The three mechanisms, in order of frequency, are: (1) paternal deletion 15q11-q13 (~65–70%), (2) maternal uniparental disomy (UPD) of chromosome 15 (~25–30%) where both copies come from the mother, and (3) imprinting defects (<5%). Angelman syndrome results from the converse — loss of the maternal 15q11-q13 region (with maternal deletions being most common, or paternal UPD). The contrast between PWS and Angelman syndrome is a classical NEET PG question on genomic imprinting.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.