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.