A 28-year-old woman with a history of preterm birth to an infant with hypotonia and feeding difficulties is counseled about recurrence risk. Prenatal testing reveals the fetus has inv(15)(p11q13) — a pericentric inversion. Which molecular mechanism determines whether this fetus has Prader-Willi syndrome?
- A Size of the inversion — large inversions invariably cause genomic imbalance
- B Parental origin of the inverted chromosome — only paternally inherited deletion/inversion of 15q11-q13 causes PWS ✓
- C Whether the inversion disrupts the centromere — pericentric inversions always cause monosomy
- D The trinucleotide repeat expansion within the inverted segment
Explanation
Prader-Willi syndrome requires loss of paternally derived genes at 15q11-q13 (including SNRPN, NDN, MAGEL2 among others, which are expressed only from the paternal allele — maternal alleles are imprinted/silenced). A pericentric inversion of chromosome 15 involving 15q11-q13 only causes PWS if inherited from the father — the inverted segment disrupts paternally imprinted gene expression or creates a deletion through recombination. If maternally inherited, the same inversion produces Angelman syndrome (if UBE3A is disrupted). Parental origin is the critical determinant, not the inversion size per se.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.