title: The proportion of uniparental disomy is increased in Prader-Willi syndrome due to an advanced maternal childbearing age in Korea.
abstract: Prader-Willi syndrome (PWS) is a genetic disorder caused by the absence of expression of the paternal copy of maternally imprinted genes in chromosome region 15q11-13. The genetic subtypes of PWS are classified into deletion (~70%), maternal uniparental disomy (mUPD; 25-30%), imprinting center defects (3-5%) and rare unbalanced translocations. Recently, Matsubara et al. reported a significantly higher maternal age in a trisomy rescue (TR) or gamete complementation (GC) by nondisjunction at maternal meiosis 1 (M1) group than in a deletion group. In the present study, we try to confirm their findings in an ethnically different population. A total of 97 Korean PWS patients were classified into deletional type (n=66), TR/GC (M1) (n=15), TR/GC by nondisjunction at maternal meiosis 2 (n=2), monosomy rescue or postfertilization mitotic nondisjunction (n=4) and epimutation (n=2). Maternal ages at birth showed a significant difference between the deletion group (median age of 29, interquartile range (IQR)=(27,31)) and the TR/GC (M1) group (median age of 35, IQR=(31,38)) (P<0.0001). The relative birth frequency of the TR/GC (M1) group has substantially increased since 2006 when compared with the period before 2005. These findings support the hypothesis that the advanced maternal age at childbirth is a predisposing factor for the development of mUPD because of increased M1 errors.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Cho
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Sohn
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Maeng
authors.forename: You Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000328:Adult; D000367:Age Factors; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008423:Maternal Age; D008540:Meiosis; D018895:Microsatellite Repeats; D011218:Prader-Willi Syndrome / Q000453:epidemiology / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D024182:Uniparental Disomy / Q000235:genetics*