Homozygous SCN5A mutation in Brugada syndrome with monomorphic ventricular tachycardia and structural heart abnormalities.
OBJECTIVE
To describe a patient showing monomorphic ventricular tachycardia, ECG aspect of Brugada syndrome, and structural heart abnormalities due to a homozygous missense mutation in SCN5A.


RESULTS
Thirteen subjects (six males, seven females, mean age 46 +/- 22 years) belonging to the same family underwent physical examination, basal biochemical marker detection, 12-lead ECG, Holter ECG, signal-averaged ECG, echocardiogram and genetic analysis. The proband underwent a stress test together with left and right ventricular angiography and electrophysiological study. Three subjects (the proband, his mother, and one brother) showed on ECG an ST-segment elevation in the right precordial leads with coved type aspect. Moreover, the proband presented a sustained monomorphic ventricular tachycardia (left bundle branch block aspect with superior axis), whereas all other family members were asymptomatic. Imaging techniques documented right ventricular structural abnormalities only in the proband. Mutation screening in SCN5A gene was performed in the proband and in available family members. The proband carries a novel SCN5A mutation, R814Q, in homozygous, whereas the parents and four siblings were heterozygous carriers of the same mutation.


CONCLUSIONS
This study provides the first evidence of a homozygous missense mutation in SCN5A associated with atypical ventricular arrhythmias and right structural abnormalities.
Frigo
Gianfranco
G
Department of Cardio-Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy.
Rampazzo
Alessandra
A
Bauce
Barbara
B
Pilichou
Kalliopi
K
Beffagna
Giorgia
G
Danieli
Gian Antonio
GA
Nava
Andrea
A
Martini
Bortolo
B
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D053840:Brugada Syndrome / Q000235:genetics* / Q000503:physiopathology; D017023:Coronary Angiography; D003937:Diagnosis, Differential; D004452:Echocardiography; D004562:Electrocardiography; D005820:Genetic Testing; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000503:physiopathology
D015415:Biomarkers; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels