Prader-Willi syndrome and Angelman syndrome affect the same chromosomal region (15q11-q13) but cause distinct phenotypes based on the parental origin of the deletion. This phenomenon is explained by:

• A Mitochondrial inheritance — maternal transmission causing different phenotypes
• B Variable expressivity of the same deletion depending on sex of the child
• C Genomic imprinting — the paternal copy is expressed for genes causing PWS and the maternal copy for genes causing AS ✓
• D Anticipation — expanded trinucleotide repeat causing more severe phenotype in subsequent generations

Explanation

Prader-Willi syndrome (PWS) results from loss of paternally expressed genes at 15q11-q13 (e.g., SNRPN, NDN); Angelman syndrome (AS) results from loss of maternally expressed UBE3A at the same locus. Genomic imprinting silences one parental allele epigenetically (by DNA methylation and histone modification); the clinically expressed copy is parent-of-origin specific. Mitochondrial inheritance and trinucleotide expansion are unrelated mechanisms.

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

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Written and medically reviewed by the StethoPrep medical team.