Angelman syndrome and Prader-Willi syndrome both result from absence of the 15q11-q13 region but exhibit entirely different phenotypes. The molecular basis for this phenotypic difference is imprinting. Which of the following correctly states the gene expression pattern?

• A PWS: paternal 15q11-q13 deleted or maternal UPD15 (loss of paternally expressed genes including SNRPN/NDN); AS: maternal 15q11-q13 deleted or paternal UPD15 (loss of maternally expressed UBE3A) ✓
• B PWS: maternal deletion; AS: paternal deletion — both show loss of the same gene set but imprinting reversal
• C PWS: biallelic deletion of SNRPN causes hyperphagia; AS: biallelic expression of UBE3A causes seizures
• D PWS and AS result from the same epigenetic defect in DNA methylation imprinting centre with phenotype determined by sex of parent

Explanation

The 15q11-q13 imprinting centre contains genes expressed from only one parental chromosome. In Prader-Willi syndrome (PWS), the paternally derived genes (SNRPN, NDN, snoRNAs) are silenced — either by deletion of the paternal 15q11-q13, maternal uniparental disomy (both copies from mother), or imprinting centre defect. These paternal genes are not expressed from the maternal allele (which is imprinted/silenced). In Angelman syndrome (AS), the maternally expressed UBE3A (ubiquitin E3 ligase) gene is silenced — by maternal 15q11-q13 deletion, paternal UPD15, or imprinting centre defect. UBE3A is only expressed from the maternal allele in neurons (both alleles elsewhere). Methylation testing of 15q11-q13 distinguishes PWS and AS: PWS shows only maternal methylation pattern (absent paternal unmethylated band); AS shows only paternal pattern (absent maternal methylated band).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.