全外显子组测序在中国一个患有心律失常的家族中鉴定出一种新型SCN5A突变（C335R）。
Whole-exome sequencing identifies a Novel SCN5A mutation (C335R) in a Chinese family with arrhythmia.
作者信息
Huang Hao, Ding Dong-Bo, Fan Liang-Liang, Jin Jie-Yuan, Li Jing-Jing, Guo Shuai, Chen Ya-Qin, Xiang Rong
机构信息
1School of Life Sciences,Central South University,Changsha,China.
2Department of Cardiology,The Second Xiangya Hospital of Central South University,Changsha,China.
出版信息
Cardiol Young. 2018 May;28(5):688-691. doi: 10.1017/S1047951117002980. Epub 2018 Feb 6.
BACKGROUND
SCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.
METHODS
Genomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.Results and conclusionsA novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.
背景
SCN5A基因编码钠通道α亚基Nav1.5。SCN5A突变可导致遗传性心律失常，如3型长QT综合征和Brugada综合征。在此，我们试图在一个心律失常家族中鉴定新的突变。
方法
从一名被诊断为心房扑动的先证者血液中分离基因组DNA。进行了Illumina Hiseq 2000全外显子测序，并采用心律失常相关基因筛选策略分析致病基因。应用桑格测序法验证该突变在家族中的共分离情况。
结果与结论
鉴定出SCN5A基因中的一个新的错义突变（C335R），该突变在受影响的家庭成员中呈共分离状态。预测该错义突变会导致Na+电流峰值幅度降低，进而导致通道蛋白功能障碍。我们的研究扩展了SCN5A突变谱，并有助于心律失常家族的遗传咨询。
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