Genetic Markers of Spina Bifida: Enrichment of Pathogenic Variants and Variants of Uncertain Significance.

INTRODUCTION

The genetic diversity of the population in India, shaped by its unique history of migrations and varied ethnic landscape, suggests the possibility of genetic profiles distinct from the western populations.

OBJECTIVE

The objective is to investigate the genetic basis of spina bifida in the Indian cohort through whole-exome sequencing and pathway enrichment.

METHODS

The variants of uncertain significance (VUS) of spina bifida were identified through whole-exome sequencing in the study cohort ( = 3). The pathogenic, likely pathogenic, and VUS were analyzed for protein-protein interactions and functional associations with genes implicated in spina bifida using tools such as STRING and KEGG pathways, which were validated through a literature review. The study was focused on the Wnt/planar cell polarity signaling pathway, which is crucial for neural tube closure.

RESULTS

The study-cohort was collectively represented through 40 common VUS, including eight deleterious SNPs related to genes , , , , , , , and . These genes were functionally linked to neural development, immune response, and cellular processes critical for neural tube closure. Notably, interactions were observed between four genes , , , and ) and (Wnt signaling pathway) crucial for embryonic neural tube formation.

CONCLUSIONS

This study has identified novel genetic variants and pathways potentially contributing to the etiopathogenesis of spina bifida in the Indian population. Future research with larger cohorts and functional studies is necessary to validate these findings and explore their potential for clinical applications in spina bifida.