title: Identification of six novel SCN5A mutations in Japanese patients with Brugada syndrome.
abstract: 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.
authors.affiliation: Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Akihiro
authors.initials: A
authors.lastname: Saito
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Irie
authors.forename: Shoichi
authors.initials: S
authors.lastname: Tange
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Iso
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D053840:Brugada Syndrome / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015995:Prevalence; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels