## **Core Concept**
Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of function of genes on chromosome 15 inherited from the father. The condition is characterized by severe infantile hypotonia, poor feeding in infancy, followed by obesity and short stature. The genetic mechanisms involved include deletion, maternal uniparental disomy (UPD), and imprinting defects.

## **Why the Correct Answer is Right**
The correct answer, , refers to paternal uniparental disomy (UPD) of chromosome 15. PWS is caused by the loss of function of genes on chromosome 15 that are normally expressed from the paternal allele. Paternal UPD of chromosome 15 would actually result in two sets of paternal genes and no maternal genes, which could potentially lead to Angelman syndrome or other conditions due to the lack of maternal gene expression but not PWS.

## **Why Each Wrong Option is Incorrect**
- **Option A:** refers to a deletion on the paternal chromosome 15. This is a known cause of PWS because it leads to the loss of genes that are normally expressed from the paternal allele.
- **Option B:** refers to maternal uniparental disomy (UPD) of chromosome 15. This is a cause of PWS because it results in two maternal copies of chromosome 15 (with no paternal contribution), leading to the absence of paternally expressed genes.
- **Option C:** refers to an imprinting defect on chromosome 15. This can cause PWS by preventing the expression of genes that are normally expressed from the paternal allele.

## **Clinical Pearl / High-Yield Fact**
A key clinical pearl is that Prader-Willi syndrome and Angelman syndrome, two distinct neurodevelopmental disorders, can result from genetic abnormalities on the same chromosome (chromosome 15) but involve different parental origins of the genes. This highlights the importance of genomic imprinting in the etiology of these conditions.

## **Correct Answer: D. paternal uniparental disomy.**