Clinical polymorphism of Brugada syndrome caused by new mutation in the SCN5A gene in Afghan-Iranian family
Abstract
Introduction. Brugada syndrome (BrS) is a life-threatening arrhythmia with an autosomal dominant mode of inheritance and high risk of cardiac sudden death (SCD). Tipical ECG pat- tern characterized by incomplete right bundle-branch block and ST-segment elevations in the anterior precordial leads. The only effective treatment preventing sudden death in BrS patients is an ICD implantation.
Material and methods. Clinical and instrumental examinations for family members included 12-lead resting ECG, EchoCG, drug challenge test with a sodium channel blockers, and blood tests to evaluate level of thyroide hormone and electrolytes. Mutation testing for proband and family members was performed by capillary Sanger sequencing of the SCN5A gene.
Clinical case. Brugada syndrome was newly diagnosed in 55-year-old man after cardiac arrest with following cardiopulmonary resuscitation. A novel heterozygous nonsense mutation c.2332C>T (p.Q778*) in the SCN5A gene was identified in proband. Cascade familial screening revealed one mutation carrier out of his 4 offsprings. Proband had an ICD, and experienced 2 apropriate shocks during 2 years of follow-up. Annual check-up was recommended for his asympomatic daughter.
Discussion. We found a novel heterozygous variant p.Q778* in the SCN5A gene in a BrS patient with a strong family history of SCD. Clinical appearance of p.Q778* mutation vary significantly in this family.
Conclusion. Nowadays prognostic role of a monogenic disease-causing mutation is uncertain for BrS probands. But cascade familial screening might provide invaluable approach to identify relatives at risk, and also those who does not inherit family burden.
Keywords:Brugada syndrome, SCN5A gene, nonsense mutation, Na+ channel blocker challenge test
Clin Experiment Surg. Petrovsky J. 2018; 6 (3): 107–12.
doi: 10.24411/2308-1198-2018-13012. Received: 04.03.2018. Accepted: 10.08.2018.
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