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在CAPN2中罕见的变异增加了孤立的低可塑性左心综合征的风险

Elizabeth E Blue^1,2, Janson J White³, Michael K Dush⁴

¹Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.

|September 4, 2023

概括

隔离性低可塑性左心综合征 (iHLHS) 很少是由单基因突变引起的. 新的研究表明,CAPN2基因的变异会增加这种严重先天性心脏缺陷的风险.

科学领域:

心血管遗传学心血管遗传学
发展生物学发展生物学
遗传性心脏病研究遗传性心脏病研究

背景情况:

缺血性左心综合征 (HLHS) 是一种严重的先天性心脏缺陷 (CHD),占所有CHD的4-8%,导致25%的CHD死亡.
孤立的HLHS (iHLHS) 在70%的家庭中发生,通常没有明确的遗传原因.
尽管有大量的研究工作,但iHLHS的遗传基础在很大程度上仍然未知.

研究的目的:

为了研究孤立的低可塑性左心综合征 (iHLHS) 的遗传基础.
为了确定与iHLHS风险相关的遗传变异.
探索已识别的基因在心脏发育中的作用.

主要方法:

从四个独立的队列中对331个患有iHLHS的家庭进行了exome测序.
使用了基于孟德尔模型的分析和基于基因的关联测试.
在Xenopus laevis脊椎动物模型中进行了功能验证研究.

主要成果:

门德尔的分析表明,iHLHS通常不是由已知的CHD基因中的单个,大效应的等位基因引起的.
基因相关性测试发现与CAPN2的变异相关的iHLHS风险增加 (p = 1.8 × 10−5).
功能性研究证实了CAPN2在心室形态发生过程中的重要作用,已确定人类变异体作为低形态等位基因.

结论:

iHLHS通常不是孟德尔的情况.
CAPN2变异与增加iHLHS的风险有关.
这项研究发现了一种涉及HLHS病变的新途径,突出显示了calpain在心脏发育中的作用.

关键词:

这是Xenopus.协会协会协会协会协会有先天性心脏缺陷.发展发展发展发展发展.外基因组测序是指外基因组的测序.青青青是一个有机类产物有机基的

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