Sudden unexplained nocturnal death syndrome (SUNDS), a disorder found in 
southeast Asia, is characterized by an abnormal electrocardiogram with 
ST-segment elevation in leads V1-V3 and sudden death due to ventricular 
fibrillation, identical to that seen in Brugada syndrome. 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. Ten 
families were enrolled, and screened for mutations using single-strand DNA 
conformation polymorphism analysis, denaturing high-performance liquid 
chromatography and DNA sequencing. Mutations were identified in SCN5A in three 
families. One mutation, R367H, lies in the first P segment of the pore-lining 
region between the DIS5 and DIS6 transmembrane segments of SCN5A. A second 
mutation, A735V, lies in the first transmembrane segment of domain II (DIIS1) 
close to the first extracellular loop between DIIS1 and DIIS2, whereas the third 
mutation, R1192Q, lies in domain III. Analysis of these mutations in Xenopus 
oocytes showed that the R367H mutant channel did not express any current and the 
likely effect of this mutation is to depress peak current due to the loss of one 
functional allele. The A735V mutant expressed currents with steady state 
activation voltage shifted to more positive potentials. The R1192Q mutation 
accelerated the inactivation of the sodium channel current. Both mutations 
resulted in reduced sodium channel current (I(Na)) at a time corresponding to 
the end of phase 1 of the action potential, as described previously in the 
Brugada syndrome. Based upon these observations we suggest that SUNDS and 
Brugada syndrome are phenotypically, genetically and functionally the same 
disorder.