What is the most common genetic mechanism responsible for Prader-Willi Syndrome?

Prader-Willi Syndrome (PWS) is primarily associated with genomic imprinting and involves the loss of function of genes in a specific region of chromosome 15. The most common genetic mechanism responsible for PWS is related to a 4-6 Mb deletion on the paternal chromosome 15. This deletion affects genes that play crucial roles in development and metabolism, leading to the characteristic features of the syndrome.

The vast majority of cases, about 70%, are due to this paternal deletion, which results in the absence of gene expression from this region since the maternally inherited allele is silenced due to imprinting. This genetic alteration leads to an imbalance of gene expression and is the underlying cause of the disorder's symptoms, such as hypotonia, hyperphagia, and developmental delay.

Other mechanisms, such as paternal uniparental disomy (UPD) and imprinting defects, exist but are less common. The understanding of these different mechanisms highlights the importance of paternal contribution to the genetic landscape of Prader-Willi Syndrome, thereby emphasizing the relevance of the 4-6 Mb deletion on chromosome 15 as the predominant cause.