Key result
Novel SCN5A loss-of-function mutation links to variable familial phenotypes, from sick sinus syndrome to ventricular arrhythmias.
Why the study?
Mutations in SCN5A cause diverse cardiac phenotypes, but the clinical spectrum of loss-of-function mutations remains incompletely characterized.
Case Report (n=2)
A novel SCN5A mutation (R121W) can cause a wide spectrum of loss-of-function phenotypes, suggesting these associated disease entities should be viewed as one syndrome.
May guide SCN5A testing in mixed conduction-arrhythmia cases; leaves open R121W pathogenicity and broader implications.
Mutations in the cardiac sodium channel encoded by the gene SCN5A can result in a wide array of phenotypes. We report a case of a young male with a novel SCN5A mutation (R121W) afflicted by sick sinus syndrome, progressive cardiac conduction disorder, atrial flutter and ventricular tachycardia. His father carried the same mutation, but had a milder phenotype, presenting with progressive cardiac conduction later in life. The mutation was found to result in a loss-of-function in the sodium current. In conclusion, the same SCN5A mutation can result in a wide array of clinical phenotypes and perhaps the spectrum of SCN5A loss-of-function associated disease entities should be viewed as one syndrome.
No takes yet. Share an insight, caveat, or question.
Holst et al. (2010) conducted a case report in SCN5A mutation-associated cardiac conduction disorders and arrhythmias (n=2). SCN5A mutation (R121W) was evaluated. A novel SCN5A mutation (R121W) causing sodium current loss-of-function resulted in diverse phenotypes within a family, including sick sinus syndrome, atrial flutter, and ventricular tachycardia.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: