Prader-Willi syndrome is caused by

• A. Deletion of chromosome 7
• B. Duplication of chromosome 21
• C. Mutation on the X chromosome
• D. Lack of genetic material on chromosome 15, usually inherited from the father

Answer: (D)

Prader-Willi results from loss of function of genes on the paternal copy of chromosome 15 in the region q11-q13. In most cases this occurs because the paternal segment is deleted; in others, both copies of chromosome 15 come from the mother (maternal uniparental disomy), so the paternal genes in that region are absent because the maternal copies are silenced by imprinting. Without active paternal genes in this area, Prader-Willi manifests. A deletion on chromosome 7 causes Williams syndrome, a duplication of chromosome 21 causes Down syndrome, and a mutation on the X chromosome is associated with conditions like Rett syndrome. Thus, the lack of genetic material on chromosome 15, usually inherited from the father, best explains Prader-Willi.