Prader-Willi syndrome and Angelman syndrome are caused by abnormalities at the same chromosome 15q11-13 region but have completely different phenotypes depending on the parent of origin. Paternal uniparental disomy (UPD) of chromosome 15 would result in which syndrome?

• A Prader-Willi syndrome (both copies are paternal, lacking maternal imprinted genes that suppress appetite)
• B Beckwith-Wiedemann syndrome
• C Angelman syndrome (both copies of chromosome 15 are of paternal origin, lacking maternal imprinted expression) ✓
• D Silver-Russell syndrome

Explanation

At chromosome 15q11-13, paternally expressed genes include SNRPN and NDN, while the maternally expressed gene is UBE3A (ubiquitin ligase). Angelman syndrome requires loss of maternal UBE3A expression: paternal UPD provides two paternal copies, neither of which expresses UBE3A (normally maternally expressed), resulting in Angelman syndrome (happy puppet syndrome: intellectual disability, seizures, absent speech, microcephaly). Conversely, maternal UPD gives two maternal chromosome 15s, silencing paternal-only expressed genes (SNRPN, etc.), causing Prader-Willi syndrome.

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

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Written and medically reviewed by the StethoPrep medical team.