突变的神经元导航器 3 是一种罕见神经发育障碍的候选基因。

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-07-01 DOI:10.1002/mgg3.2473

Muhammad Umair, Meshael Alharbi, Essra Aloyouni, Abdulkareem Al Abdulrahman, Mohammed Aldrees, Abeer Al Tuwaijri, Muhammad Bilal, Majid Alfadhel

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引用次数: 0

摘要

背景：神经元导航器 3（NAV3）是神经元导航器家族（NAV1、NAV2、NAV3）蛋白之一，主要在神经系统中表达。NAV3 编码的蛋白质由具有 ATP 酶特征的保守 AAA 和线圈结构域组成，这些结构域与不同的细胞活动有关：我们描述了一名患有复杂隐性神经发育障碍（NDD）的沙特原发性患者。结果：外显子组测序（WES）发现了一个双等位基因序列，该序列与ATP酶的特征性蛋白区有关，这些蛋白区与不同的细胞活动有关：结果：WES发现NAV3基因第12外显子存在一个双等位框移变异（c.2604_2605delAG; p.Val870SerfsTer12）。此外，RT-qPCR显示患者样本中的NAV3 mRNA表达量显著下降，三维蛋白质建模显示整体二级结构被破坏：我们首次发现了导致人类 NDD 的 NAV3 基因双等位基因变异。

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Mutated neuron navigator 3 as a candidate gene for a rare neurodevelopmental disorder.

Background: Neuron navigator 3 (NAV3) is characterized as one of the neuron navigator family (NAV1, NAV2, NAV3) proteins predominantly expressed in the nervous system. The NAV3-encoded protein comprises a conserved AAA and coiled-coil domains characteristic of ATPases, which are associated with different cellular activities.

Methods: We describe a Saudi proband presenting a complex recessive neurodevelopmental disorder (NDD). Whole exome sequencing (WES) followed by Sanger sequencing, 3D protein modeling and RT-qPCR was performed.

Results: WES revealed a bi-allelic frameshift variant (c.2604_2605delAG; p.Val870SerfsTer12) in exon 12 of the NAV3 gene. Furthermore, RT-qPCR revealed a significant decrease in the NAV3 mRNA expression in the patient sample, and 3D protein modeling revealed disruption of the overall secondary structure.

Conclusion: For the time, we associate a bi-allelic variant in the NAV3 gene causing NDD in humans.

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.