Two unrelated children each have a deletion on chromosome 15q11-q13 confirmed by microarray. Child 1 has hypotonia, hyperphagia with obesity from early childhood, small hands and feet, and hypogonadism. Child 2 has severe intellectual disability, ataxia, frequent laughter, and seizures. The difference in phenotype between these two children is best explained by:

• A Difference in size of the deletion
• B Mitochondrial heteroplasmy
• C Presence of uniparental disomy in child 2 only
• D Parental origin of the deleted chromosome due to genomic imprinting ✓

Explanation

The 15q11-q13 region contains oppositely imprinted genes. Loss of the PATERNAL segment (by deletion, maternal uniparental disomy, or imprinting centre defect) causes Prader-Willi, because paternal genes SNRPN and others are needed there. Loss of the MATERNAL segment causes Angelman syndrome via loss of maternally expressed UBE3A, since the paternal UBE3A allele is normally silenced in brain. Identical deletions therefore give opposite syndromes depending on parental origin, the textbook example of imprinting.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.