Angelman syndrome and Prader-Willi syndrome both involve chromosome 15q11-q13 but differ in parent of origin. Angelman syndrome arises from:

• A Loss of paternally imprinted region (paternal deletion or maternal UPD at 15q11-q13)
• B UBE3A gain-of-function mutation on the paternal chromosome
• C Loss of maternally imprinted region (maternal deletion or paternal UPD at 15q11-q13) ✓
• D Duplication of 15q11-q13 derived from the maternal chromosome

Explanation

Angelman syndrome is caused by absence of the maternally expressed UBE3A gene (encoding an E3 ubiquitin ligase) at 15q11-q13. The paternal UBE3A allele is silenced by imprinting in neurons; therefore, loss of maternal contribution (maternal deletion ~70%, paternal uniparental disomy ~5%, UBE3A mutation ~10%) causes Angelman syndrome (happy demeanor, seizures, absent speech, ataxia). Prader-Willi syndrome results from loss of the paternally expressed region in the same locus (paternal deletion ~70%, maternal UPD ~25%), causing hypotonia, hyperphagia, and hypogonadism.

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

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Written and medically reviewed by the StethoPrep medical team.