Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease.
Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease.
复制标题
TNNI3K 中与心脏传导疾病相关的无义突变的鉴定。
DOI：
10.1002/jcla.23418
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发表时间：
2020-09
影响因子：
2.7
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Liu J;Liu D;Li M;Wu K;Liu N;Zhao C;Shi X;Liu Q
心传导疾病（CCD）是一种常见的心血管疾病，可导致危及生命的疾病。近年来，人们逐渐认识到遗传在CCD中的重要性。一些致病基因被发现与CCD有关，如SCN5A、TRPM4、SCN1B、TNNI3K、LMNA和NKX2.5。迄今为止，只有四种TNNI3K基因突变被确定与CCD有关。为了确定一个中国CCD家族的潜在致病突变，我们进行了全外显子组测序（WES）。Sanger测序证实了潜在的突变。Real - time qPCR检测TNNI3K mRNA表达水平。在该家族中发现TNNI3K无义突变（NM_015978.2: g.170891C > T, c.1441C > T），并通过Sanger测序进行验证。Real - time qPCR证实，与对照组相比，TNNI3K mRNA表达水平下降。本研究首次在一个中国家庭中发现与CCD相关的无义TNNI3K突变。携带突变的TNNI3K （c.1441C > T）暗示了一种常染色体显性遗传模式的功能丧失致病机制。本研究丰富了TNNI3K突变的表型谱，为TNNI3K突变与CCD之间的基因型-表型相关性提供了新的视角，并表明了筛查TNNI3K在CCD患者中的重要性。
Cardiac conduction disease (CCD) is a common cardiovascular disease which can lead to life‐threatening conditions. The importance of heredity in CCD has been realized in recent years. Several causal genes have been found to be implicated in CCD such as SCN5A, TRPM4, SCN1B, TNNI3K, LMNA, and NKX2.5. To date, only four genetic mutations in TNNI3K have been identified related to CCD. Whole‐exome sequencing (WES) was carried out in order to identify the underlying disease‐causing mutation in a Chinese family with CCD. The potential mutations were confirmed by Sanger sequencing. Real‐time qPCR was used to detect the level of TNNI3K mRNA expression. A nonsense mutation in TNNI3K (NM_015978.2: g.170891C > T, c.1441C > T) was identified in this family and validated by Sanger sequencing. Real‐time qPCR confirmed that the level of TNNI3K mRNA expression was decreased compared with the controls. This study found the first nonsense TNNI3K mutation associated with CCD in a Chinese family. TNNI3K harboring the mutation (c.1441C > T) implicated a loss‐of‐function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum of TNNI3K mutations, casting a new light upon the genotype‐phenotype correlations between TNNI3K mutations and CCD and indicating the importance of TNNI3K screening in CCD patients.
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影响因子：
30.8
作者：
Patterson M;Barske L;Van Handel B;Rau CD;Gan P;Sharma A;Parikh S;Denholtz M;Huang Y;Yamaguchi Y;Shen H;Allayee H;Crump JG;Force TI;Lien CL;Makita T;Lusis AJ;Kumar SR;Sucov HM
通讯作者：
Sucov HM
影响因子：
4.5
作者：
Lodder EM;Scicluna BP;Milano A;Sun AY;Tang H;Remme CA;Moerland PD;Tanck MW;Pitt GS;Marchuk DA;Bezzina CR
通讯作者：
Bezzina CR
影响因子：
3.5
作者：
Fan, Liang-Liang;Huang, Hao;Xiang, Rong
通讯作者：
Xiang, Rong
影响因子：
3.5
作者：
Theis, Jeanne L.;Zimmermann, Michael T.;Olson, Timothy M.
通讯作者：
Olson, Timothy M.
影响因子：
4.5
作者：
Gan, Peiheng;Patterson, Michaela;Sucov, Henry M.
通讯作者：
Sucov, Henry M.