PCR-Based Strategies for the Diagnosis of Prader-Willi/Angelman Syndromes

Imprinting is the naturally occurring functional inequality of alleles of a given gene reflecting their parental origin. Only one of the alleles (either maternal or paternal) is functional (producing mRNA) in an imprinted gene. Imprinted genes in the human genome have been identified and are sometimes associated with particular disorders. The two best-known conditions in human genetics that are the result of imprinted gene abnormalities are Prader-Willi (PWS) and Angelman (AS) syndromes. These two clinically distinct neurobehavioral disorders are the result of absent/deficient function of alleles of genes in the paternally (PWS) or maternally (AS) derived proximal segment of the long arm of chromosome 15 (15q11?ql3). This chromosomal region is normally imprinted. At least four genes in this region were found to be expressed only by paternally derived alleles () and the deficiency of these and possibly other gene products in the region is believed to result in Prader-Willi syndrome. One gene, UBE3A, located within the PWS/ AS region was found to be expressed in certain tissues only by its maternally derived allele. Mutations in this gene are associated with some cases of AS ().