高通量测序鉴定肥厚型心肌病患儿致病突变

目的利用目标基因靶向捕获高通量测序方法鉴定肥厚型心肌病(HCM)患儿的致病突变,分析基因型与临床表型的关系。方法对1例14岁男性HCM患儿进行血液与临床资料收集。提取其全血基因组DNA、文库制备,靶向富集8个编码肌小节蛋白的HCM的致病基因,并行高通量测序。通过生物信息学分析筛选致病突变。用1代测序来验证2代测序发现的致病突变位点。结果患儿有晕厥史,左心室严重肥厚,心电图呈传导阻滞。目标基因捕获高通量测序筛查致病突变的结果经与公共数据库和内部健康人测序数据库对比,发现致病突变位点MYH7R869C。此位点检测结果与Sanger测序结果完全一致。结论利用目标基因捕获测序技术可筛选出HCM致病突变MYH7 R869C。携带此突变的患儿临床表型严重。MYH7 R869C突变可能是我国HCM患儿的突变热点。

Research of identification of pathogenic mutations in hypertrophic cardiomyopathy by high throughput sequencing technique

Objective To identify pathogenic mutations associated with hypertrophic cardiomyopathy（ HCM） in a child by targeted capture and high throughput sequencing technique,and to study the genotype-phenotype correlation. Methods Whole blood and clinical data from a male patient of 14 years old with HCM were collected. Genomic DNA was extracted and library was prepared. Exomes of patients with 8 HCM-related genes encoding sarcomere protein were captured and sequenced. The pathogenic mutation was identified by informatics analysis and was validated by Sanger sequencing technique. Results The patient had the incidence of syncope,severe myocardial hypertrophy in left ventricle and conduction block. Targeted capture and sequencing technique were used to screen the pathogenic mutations associated with HCM. After the results were aligned with public database and in-house database,pathogenic mutations MYH7 R869C was found. The pathogenic mutation was accordant with the result analyzed by Sanger sequencing. Conclusion Pathogenic mutation MYH7 R869C can be identified in HCM by targeted capture and high throughput sequencing technique. The child with the mutation presents severe clinical phenotype. MYH7 R869C mutation might be a hot spot mutation.