title: Maternal age effect on the development of Prader-Willi syndrome resulting from upd(15)mat through meiosis 1 errors.
abstract: Prader-Willi syndrome (PWS) is primarily caused by deletions involving the paternally derived imprinted region at chromosome 15q11.2-q13 and maternal uniparental disomy 15 (upd(15)mat). The underlying mechanisms for upd(15)mat include trisomy rescue (TR), gamete complementation (GC), monosomy rescue and post-fertilization mitotic error, and TR/GC is mediated by non-disjunction at maternal meiosis 1 (M1) or meiosis 2 (M2). Of these factors involved in the development of upd(15)mat, M1 non-disjunction is a maternal age-dependent phenomenon. We studied 117 Japanese patients with PWS and identified deletions in 84 patients (Deletion group) and TR/GC type upd(15)mat through M1 non-disjunction in 15 patients (TR/GC (M1) group), together with other types of abnormalities. Maternal age was significantly higher in TR/GC (M1) group than in Deletion group (median (range), 37 (35-45) versus 30 (19-42); P=1.0 × 10(-7)). Furthermore, delayed childbearing age became obvious since the year 2003 in Japan, and relative frequency of TR/GC (M1) group was significantly larger in patients born since the year 2003 than in those born until the year 2002. The results imply that the advanced maternal age at childbirth is a predisposing factor for the development of upd(15)mat because of increased M1 errors.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsubara
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Murakami
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008423:Maternal Age; D008540:Meiosis / Q000235:genetics*; D008875:Middle Aged; D011218:Prader-Willi Syndrome / Q000145:classification / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*; D055815:Young Adult