A 5-year-old boy with Prader-Willi syndrome has no deletion at the usual site on chromosome 15. Which finding would best confirm PWS?

A 5-year-old boy with Prader-Willi syndrome has no deletion at the usual site on chromosome 15. Which finding would best confirm PWS?

• A. Deletion in the paternal chromosome 15
• B. Maternal origin of both chromosomes 15
• C. Large trinucleotide repeat expansion in the PWS area of chromosome 15
• D. Translocation in the short arm of chromosome 15

Answer: (B)

Prader-Willi syndrome results from loss of expression of paternal genes in the 15q11-q13 region. If there isn’t a deletion at the usual site, the next most characteristic mechanism is uniparental disomy, specifically two copies of chromosome 15 from the mother. With two maternal copies, the paternal genes are absent from expression, producing the PWS phenotype. Finding that both chromosome 15s are of maternal origin directly confirms this mechanism. In practice, this can be shown by genetic testing demonstrating uniparental disomy or by methylation testing in the 15q11-q13 region that reflects two maternal imprints. The other possibilities don’t fit as neatly: a paternal deletion would produce PWS but is ruled out by the scenario; a large trinucleotide repeat expansion is not associated with PWS; a translocation could disrupt genes but isn’t the most specific or typical cause.

Prader-Willi syndrome results from loss of expression of paternal genes in the 15q11-q13 region. If there isn’t a deletion at the usual site, the next most characteristic mechanism is uniparental disomy, specifically two copies of chromosome 15 from the mother. With two maternal copies, the paternal genes are absent from expression, producing the PWS phenotype. Finding that both chromosome 15s are of maternal origin directly confirms this mechanism. In practice, this can be shown by genetic testing demonstrating uniparental disomy or by methylation testing in the 15q11-q13 region that reflects two maternal imprints. The other possibilities don’t fit as neatly: a paternal deletion would produce PWS but is ruled out by the scenario; a large trinucleotide repeat expansion is not associated with PWS; a translocation could disrupt genes but isn’t the most specific or typical cause.