title: Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect.
abstract: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are neurogenetic disorders that are caused by the loss of function of imprinted genes in 15q11-q13. In a small group of patients, the disease is due to aberrant imprinting and gene silencing. Here, we describe the molecular analysis of 51 patients with PWS and 85 patients with AS who have such a defect. Seven patients with PWS (14%) and eight patients with AS (9%) were found to have an imprinting center (IC) deletion. Sequence analysis of 32 patients with PWS and no IC deletion and 66 patients with AS and no IC deletion did not reveal any point mutation in the critical IC elements. The presence of a faint methylated band in 27% of patients with AS and no IC deletion suggests that these patients are mosaic for an imprinting defect that occurred after fertilization. In patients with AS, the imprinting defect occurred on the chromosome that was inherited from either the maternal grandfather or grandmother; however, in all informative patients with PWS and no IC deletion, the imprinting defect occurred on the chromosome inherited from the paternal grandmother. These data suggest that this imprinting defect results from a failure to erase the maternal imprint during spermatogenesis.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany. karin.buiting@uni-essen.de
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gross
authors.forename: Christina
authors.initials: C
authors.lastname: Lich
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Osman
authors.initials: O
authors.lastname: el-Maarri
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics*; D001483:Base Sequence; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D017931:DNA Primers; D018392:Genomic Imprinting; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011218:Prader-Willi Syndrome / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers