Abstract

Abstract

Brugada syndrome is a genetic condition that predisposes to ventricular tachycardia. It is caused by loss of function heterozygous mutations of the SCN5A gene in 20% of patients with the condition. There is only a single report of Brugada syndrome due to a large deletion involving the whole of SCN5A in the literature. We describe a further two families with identical chromosome 3p22.2 deletions including the SCN5A and SCN10A genes only.

Affected family members had clinical features of Brugada syndrome, conduction disease, ventricular arrhythmias and sudden death. The deletion was initially identified using MLPA and array CGH. Medium coverage whole genome sequencing was used to define the breakpoints of the deletion, confirming involvement of both SCN5A and SCN10A, and that the deletions were identical in the two families. A facile PCR-based assay was developed for cascade testing of additional family members.

This report confirms that heterozygous whole gene deletions involving SCN5A cause Brugada syndrome and overlapping phenotypes. Deletion of SCN10A may also be contributing to the cardiac phenotype. This study also highlights the utility of medium coverage whole genome sequencing for defining deletion breakpoints in a diagnostic setting.