A Double Heterozygous Mutation of TNNI3 Causes Hypertrophic Cardiomyopathy in a Han Chinese Family

作者：Hua Zheng, Huajie Huang, Zhisong Ji, Qi Yang, Qiuxia Yu, Fan Shen, Cuixian Liu, Fu Xiong · 发表于：Cardiology · 年份：2015 · DOI：10.1159/000440877 · 被引用次数：8 · 研究领域：Cardiomyopathy and Myosin Studies、Protein Tyrosine Phosphatases、Nuclear Structure and Function

Objectives: To investigate the variations in the TNNI3 gene in a Chinese Han family affected by hypertrophic cardiomyopathy (HCM) and the potential molecular mechanism linking these mutations with disease. Methods: Peripheral venous blood was acquired from family members, and TNNI3 mutations were identified by DNA sequencing. The pathophysiology of TNNI3 mutations was investigated using bioinformatics, subcellular localization determination and Western blotting. Results: Sanger sequencing revealed that the proband possessed 2 heterozygous mutations, c.235C>T and c.470C>T, located at exons 4 and 6 of the TNNI3 gene. The proband (II-2) and her brother (II-1), who had been previously diagnosed with HCM, harbored both mutations whereas their healthy parents harbored only 1. Alignment of the TNNI3 amino acid sequence indicated that the two Pro residues were highly conserved across species. Subcellular localization showed that both wild-type (WT) and mutant TNNI3 proteins were localized at the cell nucleus. Western blot analysis of expression in human embryonic kidney 293T cells showed that the intracellular levels of the mutant proteins were significantly decreased compared to WT TNNI3 (p < 0.01). Conclusions:&l...

A Double Heterozygous Mutation of &lt;b&gt;&lt;i&gt;TNNI3&lt;/i&gt;&lt;/b&gt; Causes Hypertrophic Cardiomyopathy in a Han Chinese Family

A Double Heterozygous Mutation of <b><i>TNNI3</i></b> Causes Hypertrophic Cardiomyopathy in a Han Chinese Family