• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Human mutation >Heterozygous missense mutations in NFATC1 NFATC1 are associated with atrioventricular septal defect
【24h】

Heterozygous missense mutations in NFATC1 NFATC1 are associated with atrioventricular septal defect

机译：NFATC1 NFATC1中的杂合畸形突变与房室间隔缺损有关

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Abstract Atrioventricular septal defect (AVSD) may occur as part of a complex disorder (e.g., Down syndrome, heterotaxy), or as isolate cardiac defect. Multiple lines of evidence support a role of calcineurin/NFAT signaling in AVSD, and mutations in CRELD1 , a protein functioning as a regulator of calcineurin/NFAT signaling have been reported in a small fraction of affected subjects. In this study, 22 patients with isolated AVSD and 38 with AVSD and heterotaxy were screened for NFATC1 gene mutations. Sequence analysis identified three missense variants in three individuals, including a subject with isolated AVSD [p.(Ala367Val)], an individual with AVSD and heterotaxy [p.(Val210Met)], and a subject with AVSD, heterotaxy, and oculo‐auriculo‐vertebral spectrum (OAVS) [p.(Ala696Thr)], respectively. The latter was also heterozygous for a missense change in TBX1 [p.(Pro86Leu)]. Targeted resequencing of genes associated with AVSD, heterotaxy, or OAVS excluded additional hits in the three mutation‐positive subjects. Functional characterization of NFATC1 mutants documented defective nuclear translocation and decreased transcriptional transactivation activity. When expressed in zebrafish, the three NFATC1 mutants caused cardiac looping defects and altered atrioventricular canal patterning, providing evidence of their functional relevance in vivo. Our findings support a role of defective NFATC1 function in the etiology of isolated and heterotaxy‐related AVSD.
机译：摘要的房室间隔缺损（AVSD）可以作为复杂疾病的一部分（例如，唐氏综合征，异也）或分离心脏缺损。多条证据支持AVSD中钙素/ NFAT信号传导的作用，并且在较少的受影响的受试者中据报道，CRELD1中的突变1，作为调节率调节剂的蛋白质发挥作用。在本研究中，针对NFATC1基因突变筛选22例含有AVSD和异裂的32例患者。序列分析鉴定了三个中的三种畸形变体，包括含有孤立的AVSD的受试者[p。（ALA367VAL）]，具有AVSD和异也的个体[p。（Val210met）]，以及具有AVSD，异也和Oculo-Auriculo的受试者 - 分别 - 散光（OAV）[p。（ALA696THR）]。后者也是杂合的TBX1中的致命变化。[p。（pro86leu）]。靶向与AVSD，异裂性或OAV相关的基因的重新排列在三个突变阳性受试者中排除了额外的命中。 NFATC1突变体的功能表征记录有缺陷的核转位数和降低转录转移活性。当在斑马鱼中表达时，三个NFATC1突变体导致心脏循环缺陷和改变的房地产运河图案化，提供了体内功能相关的证据。我们的研究结果支持缺陷的NFATC1功能在孤立和异教相关的AVSD的病因中的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号