introductionNeurodevelopmental 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.

methodsIn 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.

resultsA novel biallelic missense variant in the NAV3 (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 NAV3 adds a new layer to our understanding of its potential contribution to autosomal recessive neurodevelopmental disorders. This case expands the mutational landscape of NAV3 and underscores its emerging significance in neurodevelopment.

conclusionThis study reports a novel NAV3 variant in association with autosomal recessive NDD, contributing to the growing body of evidence supporting the involvement of NAV3 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.