Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo, Japan.
J Hum Genet. 2011 Aug;56(8):566-71. doi: 10.1038/jhg.2011.59. Epub 2011 Jun 2.
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.
普拉德-威利综合征（PWS）主要由染色体 15q11.2-q13 上父源印迹区域缺失和母源单亲二体 15（upd(15)mat）引起。upd(15)mat 的潜在机制包括三体挽救（TR）、配子互补（GC）、单体挽救和受精后有丝分裂错误，TR/GC 由母性减数分裂 1（M1）或减数分裂 2（M2）的非分离介导。在 upd(15)mat 发展过程中涉及的这些因素中，M1 非分离是一个与母亲年龄相关的现象。我们研究了 117 名日本 PWS 患者，在 84 名患者中发现了缺失（缺失组），在 15 名患者中通过 M1 非分离发现了 TR/GC 型 upd(15)mat（TR/GC（M1）组），以及其他类型的异常。TR/GC（M1）组的母亲年龄明显高于缺失组（中位数（范围），37（35-45）比 30（19-42）；P=1.0×10(-7)）。此外，日本自 2003 年以来生育年龄延迟明显，2003 年以后出生的患者中 TR/GC（M1）组的相对频率明显大于 2002 年以前出生的患者。结果表明，由于 M1 错误增加，分娩时的高龄母亲是 upd(15)mat 发展的一个易感因素。
