摘要
目的分析中国人肥厚型心肌病患者心肌肌钙蛋白C（cTNC）的基因突变，及基因型与表型的关系。方法入选2015年2月就诊于青岛市第三人民医院的中国汉族家族性肥厚型心肌病一家系，利用靶向外显子捕获测序的方法对先证者的30个肥厚型心肌病相关的基因进行了全外显子扩增和高通量测序，进一步通过Sanger测序法在家系内及200名健康志愿者中进行验证。家系调查资料包括临床表现、体格检查、心电图及超声心动图。结果该家系发现2种基因突变，分别为cTNC（TNNC1）c．G175C杂合突变、肌球蛋白轻链激酶2（MYLK2）c．A1319G杂合突变。该家系4例有血缘关系的研究对象中2例携带TNNC1c．G175C杂合突变，该突变位点位于TNNC1的59位的谷氨酸（E）变为谷氨酰胺（Q）。1例携带MYLK2c．A1319G杂合突变，使440位的赖氨酸（K）变为精氨酸（R）。200名健康对照中未见异常。该家系先证者同时携带上述2种突变，超声心动图示室间隔及心尖部室壁增厚，运动减弱，最厚处室间隔23．3mm，有心室颤动发作史。结论cTNC是保守性极高的蛋白，其基因E59Q突变所在区域在不同种系间高度保守，可能是该肥厚型心肌病家系的致病基因突变位点。
Objective To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy （HCM）focusing on the cardiac troponin C gene TNNC1 c. G175C mutation. Methods All family members of a Chinese pedigree with hypertrophic cardiomyopathy admitted in Third People＇s Hospital of Qingdao in February 2005 and 200 healthy volunteers were included in this study. The coding exons of 30 hypertrophic cardiomyopathy associated genes were identified by whole exons amplification and high-throughput sequencing in the proband, and the identified mutation were further detected through bidirectional Sanger sequencing in all family members and 200 healthy volunteers. Pedigree analysis included clinical manifestation, physical examination, ECG and echocardiogram. Results A missense mutation c. G175C was identified in the TNNC1 gene in 2 family members, which resulted in a glutamic acid （E） to glutamine （Q） exchange at amino acid residue 59. A mutation c. A1319G was identified in the MYLK2 gene in 1 family member, which resulted in a lysine （K） to arginine （R） exchange at amino acid residue 440. These mutations were absent in 200 healthy controls. The proband carried the two kinds of mutations and expressed various clinical manifestations of heart failure and had history of ventricular tachycardia, paraxial atrial fibrillation, pacemaker implantation, electrocardiogram showed right bundle branch block and echoeardiography examination evidenced thickened interventricular septum （23.3 mm ） and apex and reduced wall motion of these segments. The daughter of the proband carried the TNNC1 c. G175C mutation and was also diagnosed with asymptomatic HCM by echocardiography with thickened interventricular septum （ 19 mm） and apex （ 15 mm）. Conclusion The novel missense mutation of TNNC1 c. G175C might be the disease-causing gene mutation in this Chinese pedigree with familiar HCM.
作者
邢晓博
刘福颂
王芳
宋雷
赵雯娜
刘杰
张克传
朱玉召
尚兴福
李荣
梁琰
Xing Xiaobo Liu Fusong Wang Fang Song Lei Zhao Wenna Lu Jie Zhang Kechuan Zhu Yuzhao Shang Xingfu Li Rong Liang Yan(Department of Cardiology, Third People＇s Hospital of Qingdao , Qingdao 266004, Chin)
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2016年第12期1020-1023,共4页
Chinese Journal of Cardiology
基金
青岛市科研计划（2015-WJZD061）
关键词
心肌病
肥厚性
肌钙蛋白C
突变
Cardiomyopathy, hypertrophic
Troponin C
Mutation
