心脏型肌球蛋白结合蛋白C基因c.2469-3_-4insAG和c.2469-5_-6insT突变与肥厚型心肌病的关系

目的 研究中国人群肥厚型心肌病(Hypertrophic cardiomyopathy，HCM)患者的致病基因突变位点，为遗传咨询提供证据。方法 对HCM先证者行26个HCM相关基因全部外显子及邻近区靶向高通量测序，对基因突变家系成员和80名健康志愿者行Sanger测序，以验证基因突变位点。采集分析HCM患者及其家系成员临床症状、体征、超声心动图、心电图等信息。结果 该家系两名成员的心脏型肌球蛋白结合蛋白C基因（cardiac myosin binding protein-C3，MYBPC3）内含子区域中均同时携带c.2469-3_-4insAG和c.2469-5_-6insT两个插入突变，该家系其余成员及80名健康志愿者中未检出异常突变基因。两名基因突变携带者均为HCM患者，且发病年龄晚，有心慌、胸闷症状，心脏超声提示室间隔肥厚。结论 基因突变功能预测，提示MYBPC3 c.2469-3_-4insAG和c.2469-5_-6insT基因突变可引起蛋白特性及剪接位点的改变，可能是家族性肥厚型心肌病的致病突变位点。

Relationship Between Cardiac Myosin Binding Protein-C3 Double Mutations and Familial Hypertrophic Cardiomyopathy

Objective To explore the disease-causing gene mutation in Chinese patients with hypertrohic cardiomyopathy (HCM), and to provide evidence for genetic counseling. Methods Exonic and the intron-exon splicing region of 26 HCM-related genes were identified by amplification and high-throughput sequencing in a proband with hypertrophic cardiomyopathy.For the proband,his family members,and 80 healthy volunteers,the identified mutation was verified by Sanger sequencing.Informations of the HCM proband and his family members,including clinical data,physical examination,echocardiography and electrocardiography were analyzed.Results Insertion mutations c.2469-3_-4insAG and c.2469-5_-6insT in the intron of the Cardiac myosin binding protein-C3 gene (MYBPC3) were identified firstly in two alive family menbers, including the proband,and failed to be detected in the rest of family members and in the 80 healthy volunteers. Two mutation carriers were diagnosed with HCM. The onset time of HCM was rather late. They had palpitation and chest tightness. The ultrasound showed that the interventricular septum was significantly thickened.Conclusion Functional analysis of the sequences suggested that the mutations might affect protein features and splice site changes.MYBPC3 c.2469-3_-4insAG and c.2469-5_-6insT gene mutations may be the pathogenic mutations of this hypertrohic cardiomyopathy family.