Prader-Willi syndrome and Angelman syndrome are caused by imprinting defects at chromosome 15q11-q13. Which molecular mechanism specifically causes Prader-Willi syndrome?

• A Loss of maternal chromosome 15q11-q13 expression, leading to absence of UBE3A (E6-AP ubiquitin ligase) in neurons
• B Trinucleotide repeat expansion in the SNRPN promoter region
• C Chromosomal translocation t(15;17) disrupting imprinting control region
• D Loss of paternal chromosome 15q11-q13 expression (deletion or maternal UPD 15), leading to absence of SNRPN, MAGEL2, and NDN gene products ✓

Explanation

Prader-Willi syndrome results from loss of the paternally expressed genes in chromosome 15q11-q13 — either by deletion of the paternal allele (70%), maternal uniparental disomy 15 (25%), or imprinting control center defects. Key paternally expressed genes include SNRPN (small nuclear ribonucleoprotein N), MAGEL2, and NDN. In contrast, Angelman syndrome results from loss of the maternally expressed UBE3A gene (the paternal allele is epigenetically silenced in neurons). Both chromosomal regions are governed by the same imprinting center.

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

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Written and medically reviewed by the StethoPrep medical team.