Xing X B, Liu F S, Wang F, Song L, Zhao W N, Liu J, Zhang K C, Zhu Y Z, Shang X F, Li R, Liang Y
*Department of Cardiology, Third People's Hospital of Qingdao, Qingdao 266004, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2016 Dec 24;44(12):1020-1023. doi: 10.3760/cma.j.issn.0253-3758.2016.12.006.
To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM )focusing on the cardiac troponin C gene TNNC1 c. G175C mutation. 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 bi-directional Sanger sequencing in all family members and 200 healthy volunteers. Pedigree analysis included clinical manifestation, physical examination, ECG and echocardiogram. 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 echocardiography 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). The novel missense mutation of TNNC1 c. G175C might be the disease-causing gene mutation in this Chinese pedigree with familiar HCM.
以心肌肌钙蛋白C基因TNNC1 c.G175C突变为重点，研究中国家族性肥厚型心肌病（HCM）的基因型-表型相关性。纳入2005年2月在青岛市第三人民医院收治的一个中国肥厚型心肌病家系的所有家庭成员以及200名健康志愿者。先证者通过全外显子扩增和高通量测序鉴定30个肥厚型心肌病相关基因的编码外显子，鉴定出的突变通过双向Sanger测序在所有家庭成员和200名健康志愿者中进一步检测。家系分析包括临床表现、体格检查、心电图和超声心动图。在2名家庭成员的TNNC1基因中鉴定出一个错义突变c.G175C，导致氨基酸残基59处的谷氨酸（E）替换为谷氨酰胺（Q）。在1名家庭成员的MYLK2基因中鉴定出一个突变c.A1319G，导致氨基酸残基440处的赖氨酸（K）替换为精氨酸（R）。这些突变在200名健康对照中不存在。先证者携带这两种突变，表现出各种心力衰竭的临床表现，有室性心动过速、近轴心房颤动、起搏器植入史，心电图显示右束支传导阻滞，超声心动图检查显示室间隔（23.3mm）和心尖增厚，这些节段的壁运动减弱。先证者的女儿携带TNNC1 c.G175C突变，经超声心动图检查也被诊断为无症状HCM，室间隔（19mm）和心尖（15mm）增厚。TNNC1 c.G175C这种新的错义突变可能是这个中国家族性HCM家系的致病基因突变。
