Mutations in SCN5A are linked to Brugada syndrome in approximately 20% of all 
cases (BrS1). Several dozen distinct SCN5A mutations in BrS1 have been 
associated with the increased risk of cardiac arrhythmias. However, the 
genotype-phenotype relationship remains elusive. The current study analyzed the 
SCN5A gene to elucidate the potential variability of clinical features in 
Japanese BrS1 subjects. Subjects of the present study included 30 probands (25 
male subjects, 45 ± 15 years of age) with Brugada-pattern ECG. Seven patients 
had been resuscitated from cardiopulmonary arrest (CPA group). Another 10 
patients had a history of syncope (Sy group), and 13 more remain asymptomatic 
(Asy group). We identified 8 different SCN5A mutations, including 6 novel 
mutations (CPA group: 1/7, Sy group: 3/10, Asy group: 4/13). An A735E mutation 
(located at segment (S)1 in domain (D)2) was identified in the CPA group. A 
novel splice acceptor site mutation (c.393-1c>t), which may produce a 
prematurely truncated protein, was identified in the Sy group. An E1784K 
mutation (C-terminus) and a novel mutation V1951M (C-terminus) were also 
identified in the Sy group. Four novel missense mutations, A586T (D1-D2 linker), 
R689H (D1-D2 linker), S1553R (S1-S2 in D4), and Q1706H (S5-Pore in D4) were 
identified in the Asy group. These data may help us understand the genetic 
heterogeneity of BrS1, which is more prevalent in Japanese than in whites and 
other ethnic groups.