Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve.
Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve.
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DOI：
10.1038/pr.2014.67
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发表时间：
2014-08
影响因子：
3.6
通讯作者：
Garg V
中科院分区：
文献类型：
--
作者：
Bonachea EM;Chang SW;Zender G;LaHaye S;Fitzgerald-Butt S;McBride KL;Garg V
二尖瓣主动脉瓣（BAV）是最常见的先天性心脏缺陷（CHD），并提出了遗传病因。BAV可分为左-右（R-L）尖融合伴冠心病加重，右-非冠状动脉尖（R-NC）融合伴主动脉瓣功能障碍。小鼠编码心脏转录因子的Gata5的缺失导致部分渗透的R-NC BAV，我们假设Gata5的突变与人类的R-NC BAV有关。采用Sanger测序方法对78例BAV患者（其中50例为孤立BAV， 28例为相关主动脉缩窄）进行分析，以确定GATA5序列变异。进行生化分析以鉴定鉴定的序列变异的功能缺陷。我们发现了两个罕见的杂合非同义变异，p.Gln3Arg和p.Leu233Pro，频率为2.6%（2/78）。两个非同义变异的个体都有BAV和主动脉缩窄，一个R-L和一个R-NC亚型。在非同义变体中，只有p.Gln3Arg在体外表现出转录活性下降。罕见的GATA5序列变异与人类BAV有关。我们的研究结果表明，基因型-表型与冠心病相关，但与尖端融合无关。
Bicuspid aortic valve (BAV) is the most common congenital heart defect (CHD) and has a proposed genetic etiology. BAV is categorized by cusp fusion with Right-Left (R-L) cusp fusion being associated with additional CHD and Right-Noncoronary cusp (R-NC) fusion being associated with aortic valve dysfunction. Loss of murine Gata5, which encodes a cardiac transcription factor, results in a partially penetrant R-NC BAV, and we hypothesize that mutations in GATA5 are associated with R-NC BAV in humans. A cohort of 78 BAV patients (50 with isolated BAV and 28 with associated aortic coarctation) was analyzed using Sanger sequencing to identify GATA5 sequence variants. Biochemical assays were performed to identify functional deficits of identified sequence variants. We identified two rare heterozygous non-synonymous variants, p.Gln3Arg and p.Leu233Pro, for a frequency of 2.6% (2/78). Both individuals with non-synonymous variants had BAV and aortic coarctation, one R-L and one R-NC subtype. Of the non-synonymous variants, only p.Gln3Arg demonstrated decreased transcriptional activity in vitro. Rare sequence variants in GATA5 are associated with human BAV. Our findings suggest a genotype-phenotype correlation in regards to associated CHD but not cusp fusion.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
24
作者：
Fernandez, Borja;Duran, Ana C.;Sans-Coma, Valentin
通讯作者：
Sans-Coma, Valentin
影响因子：
3.7
作者：
Thomas PS;Sridurongrit S;Ruiz-Lozano P;Kaartinen V
通讯作者：
Kaartinen V
新型 GATA5 功能丧失突变是家族性心房颤动的基础
DOI：
10.6061/clinics/2012(12)08
发表时间：
2012-12
期刊：
Clinics (Sao Paulo, Brazil)
影响因子：
--
作者：
Gu JY;Xu JH;Yu H;Yang YQ
通讯作者：
Yang YQ
影响因子：
64.8
作者：
Garg, V;Muth, AN;Srivastava, D
通讯作者：
Srivastava, D