Identification of a novel GJA3 mutation in a large Chinese family with congenital cataract using targeted exome sequencing.
Identification of a novel GJA3 mutation in a large Chinese family with congenital cataract using targeted exome sequencing.
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使用靶向外显子组测序鉴定中国先天性白内障大家庭中的新 GJA3 突变
DOI：
10.1371/journal.pone.0184440
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Yao Y;Zheng X;Ge X;Xiu Y;Zhang L;Fang W;Zhao J;Gu F;Zhu Y
常染色体显性遗传性先天性白内障（Autosomal dominant congenital cataract，ADCC）是一种临床和遗传异质性的儿童眼病，可导致严重的视力障碍甚至失明。靶向外显子组测序（TES）是遗传病基因诊断的有效方法。在本研究中，我们使用一个定制的TES面板，以确定一个四代中国家庭的遗传缺陷，双侧粉状核性白内障。在GJA 3中发现了一个新的杂合错义突变c.443C>T（p.T148I）。生物信息学分析结果表明，该突变对GJA 3编码的Cx46的结构和半通道功能有害。构建表达野生型和突变型人Cx46的质粒，并在人透镜上皮细胞（HLEC）或人胚肾（HEK-293）细胞中异位表达。荧光图像显示突变蛋白在细胞质中聚集的信号，并且在T148 I稳定细胞系中也检测到更高的蛋白水平。综上所述，我们在ADCC的GJA 3中发现了一个新的突变，这为ADCC的致病机制提供了分子见解。
Autosomal dominant congenital cataract (ADCC) is a clinically and genetically heterogeneous ocular disease in children that results in serious visual impairments or even blindness. Targeted exome sequencing (TES) is an efficient method used for genetic diagnoses of inherited diseases. In the present study, we used a custom-made TES panel to identify the genetic defect of a four-generation Chinese family with bilateral pulverulent nuclear cataracts. A novel heterozygous missense mutation c.443C>T (p. T148I) in GJA3 was identified. The results of the bioinformatic analysis showed that the mutation was deleterious to the structure and hemichannel function of Cx46 encoded by GJA3. Plasmids expressing wild-type and mutant human Cx46 were constructed and ectopically expressed in human lens epithelial cells (HLECs) or human embryonic kidney (HEK-293) cells. Fluorescent images indicated aggregated signals of mutant protein in the cytoplasm, and a higher protein level was also detected in T148I stable cell lines. In summary, we identified a novel mutation in GJA3 for ADCC, which provided molecular insights into the pathogenic mechanism of ADCC.
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影响因子：
4
作者：
Banks EA;Toloue MM;Shi Q;Zhou ZJ;Liu J;Nicholson BJ;Jiang JX
通讯作者：
Jiang JX
影响因子：
13.7
作者：
Haargaard, B;Wohlfahrt, J;Melbye, M
通讯作者：
Melbye, M
影响因子：
3.7
作者：
DeRosa AM;Meşe G;Li L;Sellitto C;Brink PR;Gong X;White TW
通讯作者：
White TW
影响因子：
4
作者：
Beyer EC;Berthoud VM
通讯作者：
Berthoud VM
通过靶向下一代测序鉴定出与常染色体显性先天性白内障相关的新型 Cx50 (GJA8) p.H277Y 突变
DOI：
10.1007/s00417-015-3019-x
发表时间：
2015-06-01
影响因子：
2.7
作者：
Chen, Chong;Sun, Qiao;Xu, Xun
通讯作者：
Xu, Xun