1例伴局灶节段性肾小球硬化的MELAS综合征家系的遗传学分析

Genetic Analysis of MELAS Syndrome Complicated with Focal Segmental Glomerular Sclerosis in a Pedigree

目的 对1例伴局性节段性肾小球硬化(FSGS)的线粒体脑肌病、乳酸酸中毒和卒中样发作(MELAS)综合征家系进行遗传学病因分析。方法 先证者,女,36岁,表现为典型的MELAS综合征伴FSGS。先证者女儿表现为癫痫发作,经临床分析考虑线粒体病的可能。应用高通量测序技术对先证者进行致病基因变异检测,利用Sanger测序对先证者及其家系成员进行验证。结果 先证者线粒体DNA检测到m.3243A>G突变,其女儿携带同样突变,但先证者母亲未检测到该突变。结论 本研究认为m.3243A>G突变是先证者MELAS表现及FSGS的分子病因,也是其女儿癫痫发作的病因。

Objective To analyze the genetic etiology of mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes(MELAS)syndrome complicated with focal segmental glomerular sclerosis(FSGS)in a pedigree.Methods The proband,female,36 years old,presented with typical MELAS syndrome with FSGS,while her daughter was suffered from epilepsy,clinical analysis showed that mitochondrial diseases could not be excluded.High throughput sequencing was used to analyze associated genetic variants of the proband.Probable pathogenic variants were validated using Sanger sequencing in the proband and related members of the pedigreem.Results m.3243A>G mutation in the mtDNA was detected in both the proband and her daughter,but not in her mother.Conclusion This study concluded that m.3243A>G mutation was the molecular etiology of the MELAS syndrome and FSGS in the proband,was also the etiology of the epilepsy in her daughter.