Imprinted regulation in the region of Prader-Willi and Angelman syndromes

Prader-Willi syndrome(PWS) and Angelman syndrome(AS) are distinct clinical phenotypes resulting from paternal and maternal deficiencies respectively in human chromosome 15qll-ql3, and are caused by deletion, uniparental disomy, or other mutations. Three paternally expressed transcripts containing small nuclear ribonucleoproteinassociated polypeptide N(SNRPN), PAR-5 and PAR-1 were absent in cultured cells from PWS patients with a small deletion that involve a differentially methylated CpG island around a 5' untranslated exon alpha of SNRPN gene. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. The small deletion, which is benign when maternally transmitted, extends upstream 50 kb from the CpG island, and results in the loss of expression of the three imprinted transcripts, altered methylation and replication timing around SNRPN gene, implying the presence of an imprinting control element.