Prader-Willi syndrome (PWS) and Angelman syndrome (AS) both result from abnormalities of chromosome 15q11-q13. The specific mechanism producing PWS when the deletion or imprinting error occurs on the PATERNAL chromosome 15 is:

• A Loss of maternally expressed MECP2, impairing neuronal development
• B Loss of paternally expressed imprinted genes (SNRPN, NDN, MKRN3, MAGEL2) in the PWS domain, with only the silenced maternal alleles remaining ✓
• C Loss of maternally expressed UBE3A (E6-AP ubiquitin ligase), causing inability to degrade target proteins in neurons
• D Uniparental disomy of maternal chromosome 15 providing double dose of imprinted maternal genes

Explanation

The PWS/AS region (15q11-q13) is controlled by genomic imprinting. In the paternal chromosome, genes in the 'PWS domain' (SNRPN, NDN, MAGEL2, MKRN3) are expressed, while the maternal copies of these are silenced (imprinted). Conversely, UBE3A is expressed from the maternal allele in neurons, and the paternal allele is silenced in neurons. Deletion of the paternal 15q11-q13 (or maternal UPD15, or imprinting defect silencing paternal alleles) causes PWS because only the silenced maternal copies of SNRPN/NDN/NDN remain — functionally equivalent to absent expression. Deletion of the maternal 15q11-q13 (or paternal UPD15) causes AS because neuronal UBE3A is lost — option C correctly describes AS, not PWS.

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

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Written and medically reviewed by the StethoPrep medical team.