https://scholars.lib.ntu.edu.tw/handle/123456789/621198
標題: | Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome | 作者: | JYH-MING JIMMY JUANG TZU-PIN LU LIANG-CHUAN LAI Ho, Chia-Chuan YEN BIN LIU CHIA-TI TSAI LIAN-YU LIN CHIH-CHIEH YU WEN-JONE CHEN FU-TIEN CHIANG Yeh, Shih-Fan Sherri LING-PING LAI Chuang, Eric Y JIUNN-LEE LIN |
關鍵字: | SUDDEN CARDIAC DEATH; ST-SEGMENT ELEVATION; J-WAVE SYNDROMES; POTASSIUM CHANNEL; MISSENSE MUTATIONS; VARIANTS; POLYMORPHISM; EXPRESSION; PROTEINS; DATABASE | 公開日期: | 23-十月-2014 | 出版社: | NATURE PUBLISHING GROUP | 卷: | 4 | 期: | 1 | 起(迄)頁: | 6733 | 來源出版物: | Scientific reports | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/621198 | ISSN: | 2045-2322 | DOI: | 10.1038/srep06733 |
顯示於: | 醫學系 |
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