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SMC5 在先天性心脏病和神经发育障碍中发挥独立作用

Matthew P O'Brien¹, Marina V Pryzhkova^2,3, Evelyn M R Lake⁴

¹Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.

International journal of molecular sciences

|January 11, 2024

概括

基因突变,不仅仅是缺氧,可以导致神经发育障碍 (NDD) 在严重先天性心脏病 (CHD) 患者. 一项研究发现,SMC5基因突变对心脏和大脑发育都有影响,这表明在心脏病中与NDD有遗传联系.

科学领域:

遗传学遗传学是一个
发展生物学发展生物学
心脏病学心脏病学

背景情况:

在多达50%的患者中,严重的先天性心脏病 (CHD) 与神经发育障碍 (NDD) 有关.
心脏手术期间或之后的缺氧是心脏病中NDD的推定原因.
最近的发现表明,心血管疾病和NDD之间存在遗传重叠,但直接证据将心血管疾病基因与独立于缺氧的NDD联系起来是有限的.

研究的目的:

研究SMC5基因在并发性CHD和NDD中的作用.
为了确定CHD相关基因的突变是否可以独立于缺氧事件引起NDD.
模拟SMC5突变对心脏和神经发育的影响.

主要方法:

一个患有低可塑性左心综合征和NDD的患者的案例研究,其新生SMC5突变.
在Xenopus tropicalis胚胎中模拟smc5突变以评估心脏和大脑发育.
在小鼠心肌细胞中对Smc5进行条件淘汰 (cKO),以评估心脏功能.
在小鼠中枢神经系统中对Smc5进行条件淘汰 (cKO),以评估大脑结构和连接性.

主要成果:

具有smc5突变的Xenopus胚胎显示心脏尺寸缩小,大脑长度减少,并破坏了pax6模式.
在小鼠心肌细胞中,SMC5 cKO导致成熟心肌细胞枯竭和异常收缩性.
在小鼠大脑中的SMC5 cKO导致大脑体积减少和运动功能连接受损,而不会影响血管或心室体积.

结论:

遗传因素,特别是SMC5等基因的突变,可以导致先天性心脏病患者的神经发育障碍.
这些发现挑战了仅仅依赖缺氧作为心脏病中NDD的原因,突出了直接的遗传联系.
SMC5在心脏和中枢神经系统发育中起着至关重要的作用,这表明并发性心脏病和NDD的共同遗传病因.

关键词:

这是心肌细胞 (cardiomyocytes).遗传性心脏病是一种先天性心脏病.功能性核磁共振成像 (MRI) 的功能性核磁共振成像功能连接性的功能连接性低可塑性左心综合征是什么神经发育的神经发育染色体的结构维护染色体的结构维护

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