Abstract 5672: Novel SCN5A Mutations and SNP in Patients with Brugada Syndrome
Background: Sodium channel alpha 5 subunit (SCN5A) mutations are important genetic abnormalities of Brugada syndrome (BS). Here we report novel SCN5A mutations in patients with BS.
Methods and Results: Genomic mutations in the SCN5A gene were analyzed by PCR and direct sequencing in 121 patients with BS (119 men and 2 women). Thirteen (11%) of the patients had SCN5A mutation and five (4%) of the patients had single nucleotide polymorphisms (SNP) associated with BS. Eleven patients had single point mutations, one patient had a deletion (1380 del N) and one patient had a mutation within the splicing junction (IVS21+1 g>a). The whole-cell patch clamp technique revealed that four novel mutations (F532C, R814Q, G833R, R878C) showed loss of function, and peak INa of a novel SNP (L1988R) transiently expressed in HEK 293 cells was significantly reduced (P<0.05). RT-PCR analysis revealed that the intronic mutation (IVS21+1 g>a) resulted in exon 21 deletion of SCN5A in cardiac biopsy specimens from the patient (Figure⇓).
Conclusions: We detected five novel SCN5A mutations (1380 del N, F532C, R814Q, G833R, R878C) and a novel disease-associated SNP (L1988R) in patients with BS. We showed a novel analysis of splicing mutation (IVS21+1 g>a) that resulted in exon skipping in the heart.