Prader-Willi syndrome and Angelman syndrome are both caused by deletions at 15q11-13 but present with completely different phenotypes depending on the parental origin of the deletion. This phenomenon is best explained by:

• A Mosaicism — the deletion affects different cell lineages in each disorder
• B Genetic anticipation — repeat expansions differ between maternally and paternally inherited alleles
• C Genomic imprinting — differential methylation silences maternal vs paternal alleles at 15q11-13 ✓
• D X-inactivation skewing depending on gender of the affected child

Explanation

Genomic imprinting at chromosome 15q11-13 means that paternal and maternal alleles are differentially expressed. The paternal allele expresses SNRPN and NDN (others silenced on maternal chromosome by methylation); deletion of the paternal allele causes Prader-Willi syndrome. The maternal allele uniquely expresses UBE3A in neurons (paternal UBE3A is silenced); deletion of the maternal allele causes Angelman syndrome. Same deletion, different parent of origin, completely different disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.