PubMed 25339316

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir1.1 , Kir5.1 , Kv2.2 , Nav1.5 , Slo2

Title: Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome.

Authors: Jyh-Ming Jimmy Juang, Tzu-Pin Lu, Liang-Chuan Lai, Chia-Chuan Ho, Yen-Bin Liu, Chia-Ti Tsai, Lian-Yu Lin, Chih-Chieh Yu, Wen-Jone Chen, Fu-Tien Chiang, Shih-Fan Sherri Yeh, Ling-Ping Lai, Eric Y Chuang, Jiunn-Lee Lin

Journal, date & volume: Sci Rep, 2014 , 4, 6733

PubMed link:

Brugada syndrome (BrS) is one of the ion channelopathies associated with sudden cardiac death (SCD). The most common BrS-associated gene (SCN5A) only accounts for approximately 20-25% of BrS patients. This study aims to identify novel mutations across human ion channels in non-familial BrS patients without SCN5A variants through disease-targeted sequencing. We performed disease-targeted multi-gene sequencing across 133 human ion channel genes and 12 reported BrS-associated genes in 15 unrelated, non-familial BrS patients without SCN5A variants. Candidate variants were validated by mass spectrometry and Sanger sequencing. Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three BrS patients (20%). Two of the three patients presented SCD and one had syncope. Interestingly, the two patients presented with SCD had compound mutations (SCNN1A:Arg350Gln and KCNB2:Glu522Lys; SCNN1A:Arg597* and KCNJ16:Ser261Gly). Importantly, two SCNN1A mutations were identified from different families. The KCNT1:Arg1106Gln mutation was identified in a patient with syncope. Bioinformatics algorithms predicted severe functional interruptions in these four mutation loci, suggesting their pivotal roles in BrS. This study identified four novel BrS-associated genes and indicated the effectiveness of this disease-targeted sequencing across ion channel genes for non-familial BrS patients without SCN5A variants.