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.
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。