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.
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Acknowledgements
The study was supported by the Korea Healthcare Technology R&D Project funded by the Ministry of Health, Welfare and Family Affairs, Republic of Korea (grant number A080588), the Samsung Biomedical Research Institute (grant number C-A9-240-3) and the In-Sung Foundation for Medical Research.
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Yoon Cho, S., Ki, CS., Bae Sohn, Y. et al. The proportion of uniparental disomy is increased in Prader–Willi syndrome due to an advanced maternal childbearing age in Korea. J Hum Genet 58, 150–154 (2013). https://doi.org/10.1038/jhg.2012.148
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DOI: https://doi.org/10.1038/jhg.2012.148
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