title: A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome.
abstract: We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype-phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy-six non-related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild-type probands. There were non-significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.
authors.affiliation: Department of Clinical Analysis, Virgen de la Arrixaca University Hospital, Murcia, Spain. espegms@gmail.com
authors.forename: E
authors.initials: E
authors.lastname: García-Molina
authors.forename: J
authors.initials: J
authors.lastname: Lacunza
authors.forename: F
authors.initials: F
authors.lastname: Ruiz-Espejo
authors.forename: M
authors.initials: M
authors.lastname: Sabater
authors.forename: A
authors.initials: A
authors.lastname: García-Alberola
authors.forename: J R
authors.initials: JR
authors.lastname: Gimeno
authors.forename: F
authors.initials: F
authors.lastname: Cañizares
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: P
authors.initials: P
authors.lastname: Martínez
authors.forename: M
authors.initials: M
authors.lastname: Valdés
authors.forename: I
authors.initials: I
authors.lastname: Tovar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053840:Brugada Syndrome / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human