高通量测序技术检测肥厚型心肌病致病基因研究

目的:利用高通量测序技术对肥厚型心肌病(HCM)患者进行基因筛查,并与临床表型相对照,以期对临床诊治HCM提供参考依据。方法:对19例门诊HCM患者进行高通量测序,检测其突变类型并收集临床资料。结果:19例患者中有9例发现基因突变,除2例患者为单磷酸腺苷(AMP)激活蛋白激酶γ2调节亚基(PRKAG2)突变外,大部分基因突变为肌节蛋白基因突变。此外,检测出2例双基因突变患者,涉及PRKAG2与肌球蛋白结合蛋白C(MYBPC3)、MYBPC3与β-重链肌球蛋白(MYH7)双基因突变。基因突变的检出率为47%。MYH7基因突变患者发病年龄相对较轻,心肌肥厚程度较重,2例PRKAG2基因突变患者均有不同程度的心肌肥厚和传导阻滞的表现。结论:高通量测序技术准确、高效,对于HCM致病基因的检测阳性率高,与临床表型相对照,对于HCM的发生、发展以及转归提供了有利的依据。

Screening pathogenic gene mutation of hypertrophic cardiomyopathy by high throughput sequencing technology

Objective To screen the pathogenic gene mutation of patients with hypertrophic cardiomyopathy （HCM） by high throughput sequencing technology and studying the genotype-phenotype correlation. Methods Nineteen patients with HCM were enrolled and tested by high throughput sequencing technology , clinical materials were analyzed with regard to genotype. Results Mutation was found in nine out of nineteen HCM patients. Most of them were sarcomere protein mutation with the exception of two cases with mutation of adenosine 5-monophosphate-aetivated protein kinase γ2 subunit （PRKA G2）. Besides, two cases with double mutations were identified , referring to PRKA G2 and MYBPC3, and MYBPC3 and heavy chain myosin 7 （MYHT）. The detection rate of gene mutation was 47%. The patients of MYH7 mutation presented a younger onset age and more serious myocardial hypertrophy,while varying degrees of conduction block and myocardial hypertrophy could be found in 2 PRKAG2 mutation patients. Conclusions High throughput sequencing technology can be used as a high performance and efficient method for screening HCM mutation. It provides a promising opportunity for further research on the nature of HCM with genotype-phenotype analysis.