家族性扩张型心肌病患儿TTN基因变异分析

Analysis of TTN gene mutation in familial dilated cardiomyopathy in children

目的探讨家族性扩张性心肌病TTN基因变异特点。方法采集1例确诊家族性扩张性心肌病6岁男性患儿及其有家族性扩张型心肌病母亲,以及无家族性扩张型心肌病史的父亲、祖父母及其外祖母的血样,提取基因组DNA。应用二代测序技术检测患儿213个心血管病相关基因,并通过生物信息分析确定可疑位点后行Sanger一代测序验证。结果患儿携带第2号染色体TTN基因三位点c.53498A>T(p.Tyr17833Phe)、c.66590G>A(p.Arg22197Gln)和c.8434G>C(p.Val2812Leu)的3种错义变异,经蛋白质功能预测,变异均可影响蛋白质功能表达。结论首次发现TTN基因c.53498A>T、c. 66590 G>A和c. 8434 G>C三个变异位点。

Objective To explore the characteristics of TTN gene mutation in familial dilated cardiomyopathy.Method The blood samples were collected from a 6-year-old boy with confirmed familial dilated cardiomyopathy and his mother who had familial dilated cardiomyopathy with familial dilated cardiomyopathy,as well as his father,grandparents and his maternal grandmothers without who didn’t have familial dilated cardiomyopathy history,and genomic DNA was extracted.Nextgeneration DNA sequencing(NGS)was used to detect 213 cardiovascular disease-related genes in the child,and the suspicious sites were identified by bioinformatics analysis and then verified by Sanger sequencing.Results Three missense mutations of TTN gene on chromosome 2,c.53498A>T(p.Tyr17833Phe),c.66590G>A(p.Arg22197Gln)and c.8434G>C(p.Val2812Leu),were carried by the child.Each of the above mutation could affect the functional expression of the protein.Conclusion This is the first time to find three variants of c.53498A>T,c.66590G>A and c.8434G>C in TTN gene.