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image of NAV3 Missense Variant in a Homozygous State: Strengthening Links to Neurodevelopmental Disorder
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Abstract

Introduction

Neurodevelopmental disorders (NDDs) represent a diverse and heterogeneous group of conditions, including global developmental delay (GDD), autism spectrum disorder (ASD), and neurodevelopmental encephalopathy with epilepsy (NDEE). While these disorders often share phenotypic similarities, their underlying genetic causes can vary widely, making clinical diagnosis challenging.

Methods

In this study, we performed whole-genome sequencing (WGS) on a family having an autosomal recessive neurodevelopmental disorder. The proband (II-2) underwent WGS, followed by variant filtering through an in-house bioinformatics pipeline. Sanger sequencing and 3D protein modeling were performed to confirm the pathogenicity of the identified variant.

Results

A novel biallelic missense variant in the (c.3430T>C; p.Ser1144Pro) was detected using WGS and Sanger sequencing. Subsequently, 3D protein modeling revealed significant alterations in the secondary structure of NAV3, indicating a potential pathogenic effect.

Discussion

The identification of a novel biallelic missense variant in adds a new layer to our understanding of its potential contribution to autosomal recessive neurodevelopmental disorders. This case expands the mutational landscape of and underscores its emerging significance in neurodevelopment.

Conclusion

This study reports a novel variant in association with autosomal recessive NDD, contributing to the growing body of evidence supporting the involvement of in human neurodevelopment. Functional validation and identification of additional patients will be essential to establish definitive genotype-phenotype correlations and uncover the mechanistic pathways underlying NAV3-associated disorders.

© 2025 The Author(s). Published by Bentham Science Publishers.
 This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode.
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2025-07-24
2025-09-10

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NAV3 Missense Variant in a Homozygous State: Strengthening Links to Neurodevelopmental Disorder
Bentham Science Publishers ; https://doi.org/10.2174/0109298673367919250626005640
/content/journals/cmc/10.2174/0109298673367919250626005640
/content/journals/cmc/10.2174/0109298673367919250626005640
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  • Article Type:     Research Article
Keywords: autosomal recessive ; WES ; NAV3 ; missense mutation ; homozygous ; Neurodevelopmental disease

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