Prader-Willi syndrome (PWS) is caused by the loss of active genes on a specific region of chromosome 15, inherited from the father.
Essentially, PWS arises from issues with the genetic material on chromosome 15. Normally, individuals inherit one copy of chromosome 15 from each parent. However, the genes responsible for Prader-Willi syndrome are only actively expressed on the chromosome inherited from the father (paternal chromosome). If these paternal genes are missing or inactive, Prader-Willi syndrome develops. This loss of function can occur through several genetic mechanisms:
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Paternal Deletion (About 70% of cases): A portion of the paternal chromosome 15 that contains these critical genes is deleted. This means the individual is missing these genes entirely.
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Maternal Uniparental Disomy (UPD) (About 25-30% of cases): The individual inherits two copies of chromosome 15 from the mother and none from the father. Because the paternal genes are required for normal development, their absence leads to PWS.
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Imprinting Defect (Less than 5% of cases): In this case, the individual inherits one copy of chromosome 15 from each parent. However, the paternal copy is "switched off" (or imprinted) incorrectly. This prevents the paternal genes from being expressed, mimicking the effect of a deletion or maternal UPD.
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Rare Chromosomal Rearrangements: Very rarely, other chromosomal abnormalities can disrupt the function of genes in the Prader-Willi region.
The underlying issue, regardless of the specific genetic mechanism, is always the lack of active, functional genes on the paternal copy of chromosome 15 in the Prader-Willi region.
