A child with Prader-Willi syndrome is found to have a deletion on chromosome 15q11-q13 on the PATERNAL chromosome. His sibling with the same 15q11-q13 deletion on the MATERNAL chromosome has Angelman syndrome. This demonstrates which genetic mechanism?

• A Genomic imprinting — differential gene expression based on parental origin of allele ✓
• B Anticipation — progressive worsening of symptoms with each generation
• C Variable expressivity — different phenotypes from same mutation in the same family
• D Incomplete penetrance — not all carriers of the deletion express disease

Explanation

This is the classic example of genomic imprinting — an epigenetic phenomenon where only one parental allele is expressed for a given gene/region due to differential methylation set during gametogenesis. At 15q11-q13, paternal alleles of SNRPN and related genes are expressed (maternal alleles silenced); deletion of paternal 15q11 eliminates SNRPN expression → Prader-Willi. The maternal UBE3A gene is expressed only from the maternal allele; deletion of maternal 15q11 silences UBE3A → Angelman syndrome. Same deletion, opposite parental origin, completely different phenotypes.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.