在子宫内胎儿死亡的长QT综合征相关突变
Lia Crotti1, David J Tester, Wendy M White
1Department of Molecular Medicine, University of Pavia, and Molecular Cardiology Laboratory, Fondazione IRRCCS Policlinico S Matteo, Pavia, Italy.
JAMA
|April 11, 2013
概括
基因检测发现长QT综合征 (LQTS) 突变在3.3%的不明原因死胎. 这项研究提供了对胎儿死亡的遗传原因和死胎的潜在机制的见解.
科学领域:
- 遗传学 是一个遗传学.
- 心脏病学 心脏病学
- 周围生理学 周围生理学
背景情况:
- 死产,或子宫内胎儿死亡,影响160个怀孕中的1个,占所有围产死亡的一半.
- 尸检评估往往无法确定死胎的原因.
- 长QT综合征 (LQTS) 是一个潜在的,但未被认可的,导致死产的因素.
研究的目的:
- 研究三个最常见的LQTS相关基因 (KCNQ1,KCNH2,SCN5A) 中突变的流行率和谱.
- 确定这些遗传变异在一系列无法解释的死产病例中的作用.
主要方法:
- 追溯基因分析91个无法解释的死胎病例,使用死者组织的DNA.
- 对KCNQ1,KCNH2和SCN5A基因进行了全面的突变分析.
- 使用异质表达和补丁电生理学的鉴定突变的功能评估.
主要成果:
- 在3.3%的死胎中发现了三个错误的突变 (KCNQ1,p.A283T;KCNQ1,p.R397W;KCNH2 [1b],p.R25W),在对照中缺席.
- 这些突变表明功能丧失与子宫内LQTS类型1和2一致.
- 在另外5个案例中,发现了与潜在的前节律表型相关的罕见SCN5A变异.
结论:
- 与LQTS易感性相关的遗传变异在3.3%的不明原因死胎中被发现.
- 总体而言,8.8%的病例在体外具有导致LQTS相关离子通道功能障碍的遗传变异.
- 这些发现表明,LQTS遗传变异可能是出生死胎的重要原因之一.
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