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

Abstract

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

Keywords

• developmental delay
• frameshift variant
• loss of function
• NAV3
• NDD
• novel candidate gene