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与双性NOTCH3功能丧失相关的明显的神经现象:对于递归遗传的证据

Behnoosh Tasharrofi¹, Ali Najafi¹, Elham Pourbakhtyaran²

¹Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Molecular biology reports

|June 1, 2024

概括

同胞性NOTCH3无变体会导致一种独特的早期发病的白细胞大脑病变,这种病变是继承自体逆行模式的,与脑内自体主导动脉病变有皮下心脏病发作和白细胞大脑病变 (CADASIL) 不同.

科学领域:

遗传学遗传学是一个
神经学神经学
分子生物学分子生物学

背景情况:

NOTCH3变体与脑内自体主导动脉病变与皮质下心脏病发作和白细胞脑病变 (CADASIL) 相关.
同胞性零NOTCH3变体呈现与CADASIL不同的神经症状,表明不同的遗传模式和临床谱.

研究的目的:

划分由同卵性零NOTCH3变体引起的神经系统疾病的临床谱.
为提供进一步的证据,支持这种独特的神经疾病的自体逆向遗传模式.

主要方法:

整体外基因组测序 (WES) 用于识别具有特定神经症状的试验物中的遗传变异.
使用桑格测序的分离分析证实了发现的NOTCH3变异的遗传模式.
在无关的病例中,还发现了异构卵性NOTCH3无效变异的偶然发现.

主要成果:

一种新型的同卵性NOTCH3无变体 (c.2984delC) 在试验中被确定,该试验样本表现出活体种族性质,无氧性,认知衰退,发作和白质异常.
实验对象的血缘亲属父母被证实是该变种的异合体携带者.
三个与之无关的病例呈现了异合的NOTCH3无变异的偶然发现.

结论:

这项研究支持了早期发病的白细胞大脑病变与同卵性NOTCH3无变异相关的自体递归遗传模式.
这与CADASIL观察到的占主导地位的功能增益机制形成鲜明对比,突出显示了基因型-表型相关性.
基因分析提供了对NOTCH3相关神经系统疾病的关键见解,有助于诊断和计划生育.

关键词:

卡达西尔 (CADASIL) 是一种外体序列排序是如何进行的继承模式继承模式在白血病中,白血病缩症 (leukodystrophy) 是一种疾病.接收器,诺奇3 接收器

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