Genetic Variants Associated with Ventricular Septal Defect in Malaysia: A Scoping Review of Current Evidence and Research Gaps.

Abstract

Ventricular septal defect (VSD) is the most prevalent congenital heart defect in Malaysia; however, its genetic basis is still not well understood. We conducted a scoping review to evaluate the current evidence on VSD-associated genetic variants in the Malaysian population. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Embase from inception to June 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Original studies investigating genetic variants associated with VSD in Malaysian patients were included. Data regarding study characteristics, investigated genes, reported variants, molecular methods, and principal findings were extracted and synthesised. Out of 28 records identified, three studies met the eligibility criteria. The included studies reported variants in three genes: SMAD7, NR0B1, and NIPBL. The identified variants included synonymous substitutions and frameshift alterations that were predicted to cause premature protein truncation. However, the available evidence was limited by small sample sizes, candidate-gene approaches, and the predominance of syndromic cases. We found no nationwide or multicentre studies using high-throughput sequencing technologies. Despite the significant disease burden, the current evidence on the genetics of VSD in Malaysia remains sparse. The lack of comprehensive genomic investigations underscores the need for collaborative studies across the nation that integrate next-generation sequencing and functional validation. This would enhance our understanding of VSD pathogenesis and support future precision medicine initiatives.