Quantitative dna methylation analysis and epigenotype‐phenotype correlations in taiwanese patients with beckwith‐wiedemann syndrome

Hsiang Yu Lin, Chung Lin Lee, Sisca Fran, Ru Yi Tu, Ya Hui Chang, Dau Ming Niu, Chia Ying Chang, Pao Chin Chiu, Yen Yin Chou, Hui Pin Hsiao, Chia Feng Yang, Meng Che Tsai, Tzu Hung Chu, Chih Kuang Chuang, Shuan Pei Lin

研究成果: Article同行評審

摘要

Background: Beckwith‐Wiedemann syndrome (BWS; OMIM 130650) is a rare overgrowth syndrome with tumor predisposition resulting from the abnormal expression or function of imprinted genes of the chromosome 11p15.5 imprinting gene cluster. The aim of this study was to identify the epigenotype‐phenotype correlations of these patients using quantitative DNA methylation analysis. Methods: One hundred and four subjects with clinically suspected BWS were enrolled in this study. All of the subjects had been referred for diagnostic testing which was conducted using methylation profiling of H19‐associated imprinting center (IC) 1 and KCNQ1OT1‐associated IC2 in high‐resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between the quantitative DNA methylation status and clinical manifestations of the enrolled subjects were analyzed. Results: Among the 104 subjects, 19 had IC2 hypomethylation, 2 had IC1 hypermethylation, and 10 had paternal uniparental disomy (pUPD). The subjects with IC2 hypomethylation were characterized by significantly more macroglossia but less hemihypertrophy compared to the subjects with pUPD (p < 0.05). For 19 subjects with IC2 hypomethylation, the IC2 methylation level was significantly different (p < 0.05) between the subjects with and without features including macroglossia (IC2 methylation level: 11.1% vs 30.0%) and prenatal or postnatal overgrowth (8.5% vs 16.9%). The IC2 methylation level was negatively correlated with birth weight z score (p < 0.01, n = 19) and birth height z score (p < 0.05, n = 13). For 36 subjects with clinically diagnosed BWS, the IC2 methylation level was negatively correlated with the BWS score (r = −0.592, p < 0.01). The IC1 methylation level showed the tendency of positive correlation with the BWS score without statistical significance (r = 0.137, p > 0.05). Conclusions: Lower IC2 methylation and higher IC1 methylation levels were associated with greater disease severity in the subjects with clinically diagnosed BWS. Quantitative DNA methylation analysis using the MassARRAY assay could improve the detection of epigenotype‐phenotype correlations, which could further promote better genetic counseling and medical care for these patients.

原文English
文章編號1066
期刊Journal of Personalized Medicine
11
發行號11
DOIs
出版狀態Published - 2021 11月

All Science Journal Classification (ASJC) codes

  • 醫藥(雜項)

指紋

深入研究「Quantitative dna methylation analysis and epigenotype‐phenotype correlations in taiwanese patients with beckwith‐wiedemann syndrome」主題。共同形成了獨特的指紋。

引用此