摘要目的 探讨外显子靶向捕获二代测序技术在遗传性肌病诊断中的应用价值,分析遗传性肌病基因型-表型关联.方法 筛选与肌病相关的致病基因,设计肌病相关基因二代测序靶向捕获试剂盒Sureselect(Panel Version 1和Panel Version 2),采用外显子靶向捕获结合二代测序技术对2013年1月至2014年6月在北京大学第一医院儿科临床诊断为遗传性肌病的134例患儿进行相关基因突变检测.2013年使用Panel Version 1对77例患儿进行了基因检测,2014年更新为Panel Version 2检测了57例患儿.对134例患儿的临床资料及基因检测结果进行分析.结果 134例患儿中男89例、女45例,就诊年龄为6个月至26岁,平均6岁1个月.74例患儿确定了致病基因突变位点,基因诊断阳性率为55.22％.包括代谢性肌病1例,先天性肌病5例,肌营养不良68例[其中先天性肌营养不良1A型(MDC1A) 22例,Ullrich先天性肌营养不良(UCMD) 11例,Bethlem肌病(BM)6例,点突变导致的杜氏肌营养不良(DMD) 12例,LMNA相关先天性肌营养不良(L-CMD)5例,埃-德二氏肌营养不良(EDMD)1例,α-抗肌萎缩相关糖蛋白病(α-DG)7例,肢带型肌营养不良(LGMD)4例].结论 临床、病理分析结合靶向捕获二代测序技术为遗传性肌病的诊断提供了新的思路,即根据临床资料、生物信息学分析等综合筛选判断,以此作为确诊的主要依据.

abstractsObjective To elucidate the usefulness of next generation sequencing for diagnosis of inherited myopathy,and to analyze the relevance between clinical phenotype and genotype in inherited myopathy.Method Related genes were selected for SureSelect target enrichment system kit (Panel Version 1 and Panel Version 2).A total of 134 patients who were diagnosed as inherited myopathy clinically underwent next generation sequencing in Department of Pediatrics,Peking University First Hospital from January 2013 to June 2014.Clinical information and gene detection result of the patients were collected and analyzed.Result Seventy-seven of 134 patients (89 males and 45 females,visiting ages from 6-month-old to 26-year-old,average visiting age was 6 years and 1 month) underwent next generation sequencing by Panel Version 1 in 2013,and 57 patients underwent next generation sequencing by Panel Version 2 in 2014.The gene detection revealed that 74 patients had pathogenic gene mutations,and the positive rate of genetic diagnosis was 55.22％.One patient was diagnosed as metabolic myopathy.Five patients were diagnosed as congenital myopathy;68 were diagnosed as muscular dystrophy,including 22 with congenital muscular dystrophy 1A(MDC1A),11 with Ullrich congenital muscular dystrophy (UCMD),6 with Bethlem myopathy (BM),12 with Duchenne muscular dystrophy (DMD) caused by point mutations in DMD gene,5 with LMNA-related congenital muscular dystrophy (L-CMD),1 with Emery-Dreifuss muscular dystrophy (EDMD),7 with alpha-dystroglycanopathy (oα-DG) patients,and 4 with limb-girdle muscular dystrophy (LGMD) patients.Conclusion Next generation sequencing plays an important role in diagnosis of inherited myopathy.Clinical and biological information analysis was essential for screening pathogenic gene of inherited myopathy.