CAJ | 학술논문

目的探讨二代测序在儿童线粒体病诊断中的应用价值.方法对2012年10月至2014年2月在首都医科大学附属北京儿童医院神经内科就诊患儿根据线粒体病标准进行评分,对70例(男38例、女32例,就诊年龄为3个月至14岁)疑似线粒体病的患儿,应用二代测序进行线粒体基因全测序和(或)与线粒体结构和功能相关的核基因测序,总结和分析基因确诊病例的临床资料.结果 70例疑似线粒体病患儿中,发现线粒体基因和核基因变异21例,其中10例为线粒体基因变异、11例为核基因变异.21例中1例为非线粒体病,由CHAT基因纯合突变(p.I187T)导致的先天性肌无力综合征伴发作性呼吸暂停(CMS-EA).20例为线粒体病,其中,Leigh综合征10例,线粒体脑肌病伴乳酸酸中毒和卒中样发作综合征4例,Leber遗传性视神经病(LHON)及LHON plus 3例,线粒体DNA耗竭综合征2例,不能分类1例.10例线粒体基因变异均为点突变,分别为A3243G、G3460A、G11778A、T14484C、T14502C、T14487C.10例核基因变异线粒体病患儿中发现5个基因变异,分别为SURF1、PDHA1、NDUFV1、SUCLA2、SUCLG1,共有14种变异类型,其中7种变异类型为未报道的新突变.结论 Leigh综合征是儿童线粒体病中最常见的综合征,应用二代测序不仅能提高Leigh综合征的分子诊断水平,还可早期诊断表现不典型的线粒体综合征以及罕见的线粒体病.
목적 탐토이대측서재인동선립체병진단중적응용개치.방법 대2012년10월지2014년2월재수도의과대학부속북경인동의원신경내과취진환인근거선립체병표준진행평분,대70례(남38례、녀32례,취진년령위3개월지14세)의사선립체병적환인,응용이대측서진행선립체기인전측서화(혹)여선립체결구화공능상관적핵기인측서,총결화분석기인학진병례적림상자료.결과 70례의사선립체병환인중,발현선립체기인화핵기인변이21례,기중10례위선립체기인변이、11례위핵기인변이.21례중1례위비선립체병,유CHAT기인순합돌변(p.I187T)도치적선천성기무력종합정반발작성호흡잠정(CMS-EA).20례위선립체병,기중,Leigh종합정10례,선립체뇌기병반유산산중독화졸중양발작종합정4례,Leber유전성시신경병(LHON)급LHON plus 3례,선립체DNA모갈종합정2례,불능분류1례.10례선립체기인변이균위점돌변,분별위A3243G、G3460A、G11778A、T14484C、T14502C、T14487C.10례핵기인변이선립체병환인중발현5개기인변이,분별위SURF1、PDHA1、NDUFV1、SUCLA2、SUCLG1,공유14충변이류형,기중7충변이류형위미보도적신돌변.결론 Leigh종합정시인동선립체병중최상견적종합정,응용이대측서불부능제고Leigh종합정적분자진단수평,환가조기진단표현불전형적선립체종합정이급한견적선립체병.
Objective To explore the application value of next generation sequencing (NGS) in the diagnosis of mitochondrial disorders.Method According to mitochondrial disease criteria,genomic DNA was extracted using standard procedure from peripheral venous blood of patients with suspected mitochondrial disease collected from neurological department of Beijing Children's Hospital Affiliated to Capital Medical University between October 2012 and February 2014.Targeted NGS to capture and sequence the entire mtDNA and exons of the 1 000 nuclear genes related to mitochondrial structure and function.Clinical data were collected from patients diagnosed at a molecular level,then clinical features and the relationship between genotype and phenotype were analyzed.Result Mutation was detected in 21 of 70 patients with suspected mitochondrial disease,in whom 10 harbored mtDNA mutation,while 11 nuclear DNA (nDNA) mutation.In 21 patients,1 was diagnosed congenital myasthenic syndrome with episodic apnea due to CHAT gene p.I187T homozygous mutation,and 20 were diagnosed mitochondrial disease,in which 10 were Leigh syndrome,4 were mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes syndrome,3 were Leber hereditary optic neuropathy (LHON) and LHON plus,2 were mitochondrial DNA depletion syndrome and 1 was unknown.All the mtDNA mutations were point mutations,which contained A3243G,G3460A,G11778A,T14484C,T14502C and T14487C.Ten mitochondrial disease patients harbored homozygous or compound heterozygous mutations in 5 genes previously shown to cause disease:SURF1,PDHA1,NDUFV1,SUCLA2 and SUCLG1,which had 14 mutations,and 7 of the 14 mutations have not been reported.Conclusion NGS has a certain application value in the diagnosis of mitochondrial diseases,especially in Leigh syndrome atypical mitochondrial syndrome and rare mitochondrial disorders.