Molecular genetics and metabolism · 2016
Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lin Hsiang-Yu, Chuang Chih-Kuang, Tu Ru-Yi, Fang Yi-Ya, Su Yi-Ning, Chen Chih-Ping, Chang Chia-Ying, Liu Hsi-Che, Chu Tzu-Hung, Niu Dau-Ming, Lin Shuan-Pei
Аннотация
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder predisposing to tumorigenesis that results from abnormal expression or function of imprinted genes of chromosome 11p15.5.
METHODS: Forty-seven patients in Taiwan with clinical suspicion of BWS were referred for diagnostic testing based on methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-resolution quantitative methylation profiling.
RESULTS: Twenty-eight patients received a clinical diagnosis of BWS (the presence of 3 major features or 2 major features and at least 1 minor feature), 18 had suspected BWS (the presence of at least 1 major feature), and 1 had isolated Wilms' tumor. Nineteen patients were identified with IC2 hypomethylation (including 1 with isolated Wilms' tumor), 1 with IC1 hypermethylation, 2 with paternal uniparental disomy, and 1 with CDKN1C mutation. Several clinical features were found to be statistically different (P<0.05) between the 2 groups-clinical diagnosis of BWS (n=28) or suspected BWS (n=18)-including macroglossia, pre- or postnatal gigantism, abdominal wall defect, ear creases, facial nevus flammeus, BWS score, and the molecular diagnosis rate. Molecular lesion was detected in 81% of patients with the presence of three major features, compared with 33% and 28% of those with two or one major feature, respectively. The mean BWS score was 5.6 for 19 subjects with "IC2 hypomethylation", compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1 hypermethylation was 6 and 7, respectively.
CONCLUSIONS: The BWS score was positively correlated with the molecular diagnosis rate (P<0.01). The BWS database of epigenotype, genotype, and phenotype is expected to promote better genetic counseling and medical care of these patients.
METHODS: Forty-seven patients in Taiwan with clinical suspicion of BWS were referred for diagnostic testing based on methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-resolution quantitative methylation profiling.
RESULTS: Twenty-eight patients received a clinical diagnosis of BWS (the presence of 3 major features or 2 major features and at least 1 minor feature), 18 had suspected BWS (the presence of at least 1 major feature), and 1 had isolated Wilms' tumor. Nineteen patients were identified with IC2 hypomethylation (including 1 with isolated Wilms' tumor), 1 with IC1 hypermethylation, 2 with paternal uniparental disomy, and 1 with CDKN1C mutation. Several clinical features were found to be statistically different (P<0.05) between the 2 groups-clinical diagnosis of BWS (n=28) or suspected BWS (n=18)-including macroglossia, pre- or postnatal gigantism, abdominal wall defect, ear creases, facial nevus flammeus, BWS score, and the molecular diagnosis rate. Molecular lesion was detected in 81% of patients with the presence of three major features, compared with 33% and 28% of those with two or one major feature, respectively. The mean BWS score was 5.6 for 19 subjects with "IC2 hypomethylation", compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1 hypermethylation was 6 and 7, respectively.
CONCLUSIONS: The BWS score was positively correlated with the molecular diagnosis rate (P<0.01). The BWS database of epigenotype, genotype, and phenotype is expected to promote better genetic counseling and medical care of these patients.