Genomic imprinting explains the difference in phenotype between Prader-Willi syndrome (PWS) and Angelman syndrome (AS), both involving chromosome 15q11-q13. PWS results from lack of paternal contribution of this region because:

• A The paternal 15q11-q13 genes are imprinted (silenced) and only the maternal copy is expressed
• B Uniparental disomy of two maternal chromosomes 15 provides double the maternal gene dose
• C Deletion on the paternal chromosome 15 allows overexpression of maternally derived UBE3A
• D The maternal 15q11-q13 genes are imprinted (silenced) and only the paternal copy is expressed; loss of paternal copy leaves no active gene ✓

Explanation

In 15q11-q13, the maternal alleles of several genes (including SNRPN, NDN) are imprinted (silenced by methylation), so only the paternal alleles are expressed in neurons. In PWS, the paternal 15q11-q13 is deleted (or both chromosomes 15 are maternal — maternal UPD), leaving no active copy of these genes. In AS, the paternal UBE3A is imprinted in neurons, so deletion of maternal 15q11-q13 (or paternal UPD) silences UBE3A, causing the Angelman phenotype.

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

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Written and medically reviewed by the StethoPrep medical team.