Key result
Novel SCN5A splice variant linked to incessant VT via a truncated protein.
Why the study?
Mutations in SCN5A are associated with inherited arrhythmias, prompting investigation of the molecular defect in a patient with clinical arrhythmias.
Case Report (n=1)
The novel SCN5A splice variant c.2262+3A>T disrupts normal mRNA splicing and produces a truncated protein, contributing to the molecular basis of early-onset incessant ventricular tachycardias.
May inform genetic testing in pediatric incessant VT; extends SCN5A variant spectrum but remains hypothesis-generating.
Objective: Voltage-gated sodium channel Na v 1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Methods: Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants in vitro . Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. Results: By genetic analysis, we identified a novel splice variant c.2262+3A>T in SCN5A gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by in silico analysis. The variant retained 79 bp at the 5′ end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818 * )] could be produced as a truncated protein. Conclusion: We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.
No takes yet. Share an insight, caveat, or question.
Yin et al. (2021) conducted a case report in Incessant ventricular tachycardias (n=1). Genetic analysis (whole-exome sequencing, minigene assay, RT-PCR, Western blot) was evaluated on Identification and functional characterization of SCN5A gene variant. A novel splice variant c.2262+3A>T in the SCN5A gene was identified in a boy with incessant ventricular tachycardias, which disturbed normal mRNA splicing and caused a truncated protein.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: