We can confirm that some Brugada syndrome patients without exonic mutations in SCN5A had no other SCN5A abnormalities, including any involving the location of the SCN5A protein.
We previously used positional cloning to identify a new locus on chromosome 3p24 in a large family with Brugada syndrome and excluded SCN5A as a candidate gene.
We have identified a novel threonine-to-isoleucine missense mutation at position 353 (T353I) adjacent to the pore-lining region of domain I of the cardiac sodium channel (SCN5A) in a family with Brugada syndrome.
In summary, this is the first report of a dysfunctional sodium channel created by an intronic mutation giving rise to cryptic splice site activation in SCN5A in a family with the BS.
Mutations in the gene encoding the human cardiac sodium channel (SCN5A) have been associated with three distinct cardiac arrhythmia disorders: the long QT syndrome, the Brugada syndrome and cardiac conduction disease.
We screened patients with SUNDS for mutations in SCN5A, the gene known to cause Brugada syndrome, as well as genes encoding ion channels associated with the long-QT syndrome.
This study reports the changes in functional expression and cellular localization of an SCN5A double mutant (R1232W/T1620M) recently discovered in patients with Brugada syndrome.
These three new SCN5A mutations in Brugada syndrome patients are all located within domain I of SCN5A, a region not previously considered important in the development of ventricular arrhythmias.