A newborn with normal karyotype presents with hypotonia, small hands and feet, almond-shaped eyes, and later develops hyperphagia and obesity. Molecular analysis shows deletion on the paternal chromosome 15q11-q13. The mechanism explaining why the same deletion on the maternal chromosome produces a completely different phenotype (Angelman syndrome) is:
- A Genomic imprinting — differential expression of maternal versus paternal alleles ✓
- B X-linked inheritance with dosage compensation
- C Variable expressivity due to modifier genes on chromosome 15
- D Mitochondrial inheritance with maternal transmission
Correct answer: A. Genomic imprinting — differential expression of maternal versus paternal alleles
Explanation
Prader-Willi syndrome (paternal 15q11-q13 deletion) and Angelman syndrome (maternal 15q11-q13 deletion) are the classic examples of genomic imprinting — an epigenetic phenomenon where gene expression from a specific chromosomal region depends on the parent of origin. In 15q11-q13, paternal genes (SNRPN cluster) are normally expressed and maternal UBE3A is expressed; when the paternal region is deleted, Prader-Willi results; when the maternal UBE3A is absent (deletion or imprinting defect), Angelman syndrome occurs.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.