title: Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes.
abstract: The D15S9 and D15S63 loci in the Prader-Willi/Angelman syndrome region on chromosome 15 are subject to parent-of-origin-specific DNA methylation. We have found two Prader-Willi syndrome families in which the patients carry a maternal methylation imprint on the paternal chromosome. In one of these families, the patients have a small deletion encompassing the gene for the small nuclear ribonucleoprotein polypeptide N, which maps 130 kb telomeric to D15S63. Furthermore, we have identified a pair of nondeletion Angelman syndrome sibs and two isolated Angelman syndrome patients who carry a paternal methylation imprint on the maternal chromosome. These Angelman and Prader-Willi syndrome patients may have a defect in the imprinting process in 15q11-13. We propose a model in which a cis-acting mutation prevents the resetting of the imprinting signal in the germ line and thus disturbs the expression of imprinted genes in this region.
authors.affiliation: Institut für Humangenetik, Freie Universität, Berlin.
authors.forename: A
authors.initials: A
authors.lastname: Reis
authors.forename: B
authors.initials: B
authors.lastname: Dittrich
authors.forename: V
authors.initials: V
authors.lastname: Greger
authors.forename: K
authors.initials: K
authors.lastname: Buiting
authors.forename: M
authors.initials: M
authors.lastname: Lalande
authors.forename: G
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: M
authors.initials: M
authors.lastname: Anvret
authors.forename: B
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004247:DNA / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008745:Methylation; D008957:Models, Genetic; D009154:Mutation; D011218:Prader-Willi Syndrome / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D005819:Genetic Markers; D004247:DNA