PDF(Pubmed)
Abstract：
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.
CONCLUSIONS: For the time, we associate a bi-allelic variant in the NAV3 gene causing NDD in humans.
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.
CONCLUSIONS: For the time, we associate a bi-allelic variant in the NAV3 gene causing NDD in humans.
摘要：
背景：神经元导航器3（NAV3）的特征是主要在神经系统中表达的神经元导航器家族（NAV1，NAV2，NAV3）蛋白之一。NAV3编码的蛋白质包含ATPases的保守AAA和卷曲螺旋结构域，它们与不同的细胞活动有关。
方法：我们描述了一个沙特先证者，他提出了一种复杂的隐性神经发育障碍（NDD）。全外显子组测序（WES），然后进行Sanger测序，进行3D蛋白建模和RT-qPCR。
结果：WES揭示了NAV3基因外显子12中的双等位基因移码变体（c.2604_2605delAG；p.Val870SerfsTer12）。此外，RT-qPCR显示患者样品中NAV3mRNA表达显著降低，和3D蛋白质建模揭示了整体二级结构的破坏。
结论：当时，我们将NAV3基因中的双等位基因变异体关联在人类中引起NDD。
方法：我们描述了一个沙特先证者，他提出了一种复杂的隐性神经发育障碍（NDD）。全外显子组测序（WES），然后进行Sanger测序，进行3D蛋白建模和RT-qPCR。
结果：WES揭示了NAV3基因外显子12中的双等位基因移码变体（c.2604_2605delAG；p.Val870SerfsTer12）。此外，RT-qPCR显示患者样品中NAV3mRNA表达显著降低，和3D蛋白质建模揭示了整体二级结构的破坏。
结论：当时，我们将NAV3基因中的双等位基因变异体关联在人类中引起NDD。
