一例ETFDH基因复合杂合新变异导致的脂质沉积性肌病

Analysis of ETFDH gene variation in a Chinese family affected with lipid storage myopathy

目的对1个中国汉族迟发型脂质沉积性肌病家系进行相关致病性基因分析,确定其致病原因,为家系遗传咨询提供依据.方法应用二代测序技术(肌病检测Panel)对先证者进行变异筛查,发现EDFTH基因可疑致病位点后,应用直接双向测序技术对该家系的两例患者及其父亲进行EDFTH基因变异分析,并在100名正常对照进行新变异验证.结果家系中2例患者均检测出EDFTH基因c.770A>G(p.Tyr257Cys)杂合变异和c.1395dupT(p.Gly466Tryfs)杂合变异,其父亲仅检测到c.770A>G(p.Tyr257Cys)杂合变异,在100名正常对照中均未检测到c.1395dupT(p.Gly466Tryfs)变异,c.1395dupT(p.Gly466Tryfs)为未报道过的新变异.结论EDFDH基因变异是该家系的致病原因,新变异的检出丰富了EDFDH基因变异谱.

Objective To detect potential variation in an ethnic Han Chinese family affected with lateonset lipid storage myopathy.Methods Next generation sequencing(NGS)was used to screen diseaserelated genes in the proband.Suspected mutation was validated with PCR and Sanger sequencing in two patients,their father,and 100 healthy controls.Results Heterozygous c.770A>G(p.Tyr257Cys)and c.1395dupT(p.Gly466Tryfs)mutation were detected in the two patients.Their father was found to be heterozygous for the c.770A>G(p.Tyr257Cys)mutation,while the c.1395dupT(p.Gly466Tryfs)variation was not reported previously and not found among the healthy controls.Conclusion Mutations of the ETFDH gene probably underlie the pathogenesis in this family.The novel c.1395dupT(p.Gly466Tryfs)has enriched the mutation spectrum of EDFDH gene.