Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms

Ling Ping Lai, Yi Ning Su, Fu Tien Chiang, Jyh Ming Juang, Yen Bin Liu, Yi Lwun Ho, Wen Jone Chen, San Jou Yeh, Chun Chieh Wang, Yu Lin Ko, Tsu Juey Wu, Kwo Chang Ueng, Meng Huan Lei, Hsuan Ming Tsao, Shih Ann Chen, Tin Kwang Lin, Mei Hwan Wu, Huey Ming Lo, Shoei K.Stephen Huang, Jiunn Lee Lin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.

Original languageEnglish
Pages (from-to)490-496
Number of pages7
JournalJournal of Human Genetics
Volume50
Issue number9
DOIs
Publication statusPublished - Sep 1 2005
Externally publishedYes

Fingerprint

Long QT Syndrome
Sodium Channels
Potassium Channels
Single Nucleotide Polymorphism
High Pressure Liquid Chromatography
Mutation
Genes
Nucleic Acid Heteroduplexes
Brugada Syndrome
DNA Sequence Analysis
Pharmaceutical Preparations
Cardiac Arrhythmias
Healthy Volunteers
Polymerase Chain Reaction

Keywords

  • K-channel
  • Long QT syndrome
  • Na-channel
  • Sudden death

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms. / Lai, Ling Ping; Su, Yi Ning; Chiang, Fu Tien; Juang, Jyh Ming; Liu, Yen Bin; Ho, Yi Lwun; Chen, Wen Jone; Yeh, San Jou; Wang, Chun Chieh; Ko, Yu Lin; Wu, Tsu Juey; Ueng, Kwo Chang; Lei, Meng Huan; Tsao, Hsuan Ming; Chen, Shih Ann; Lin, Tin Kwang; Wu, Mei Hwan; Lo, Huey Ming; Huang, Shoei K.Stephen; Lin, Jiunn Lee.

In: Journal of Human Genetics, Vol. 50, No. 9, 01.09.2005, p. 490-496.

Research output: Contribution to journalArticle

Lai, LP, Su, YN, Chiang, FT, Juang, JM, Liu, YB, Ho, YL, Chen, WJ, Yeh, SJ, Wang, CC, Ko, YL, Wu, TJ, Ueng, KC, Lei, MH, Tsao, HM, Chen, SA, Lin, TK, Wu, MH, Lo, HM, Huang, SKS & Lin, JL 2005, 'Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms', Journal of Human Genetics, vol. 50, no. 9, pp. 490-496. https://doi.org/10.1007/s10038-005-0283-3
Lai, Ling Ping ; Su, Yi Ning ; Chiang, Fu Tien ; Juang, Jyh Ming ; Liu, Yen Bin ; Ho, Yi Lwun ; Chen, Wen Jone ; Yeh, San Jou ; Wang, Chun Chieh ; Ko, Yu Lin ; Wu, Tsu Juey ; Ueng, Kwo Chang ; Lei, Meng Huan ; Tsao, Hsuan Ming ; Chen, Shih Ann ; Lin, Tin Kwang ; Wu, Mei Hwan ; Lo, Huey Ming ; Huang, Shoei K.Stephen ; Lin, Jiunn Lee. / Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms. In: Journal of Human Genetics. 2005 ; Vol. 50, No. 9. pp. 490-496.
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abstract = "Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.",
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T1 - Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms

AU - Lai, Ling Ping

AU - Su, Yi Ning

AU - Chiang, Fu Tien

AU - Juang, Jyh Ming

AU - Liu, Yen Bin

AU - Ho, Yi Lwun

AU - Chen, Wen Jone

AU - Yeh, San Jou

AU - Wang, Chun Chieh

AU - Ko, Yu Lin

AU - Wu, Tsu Juey

AU - Ueng, Kwo Chang

AU - Lei, Meng Huan

AU - Tsao, Hsuan Ming

AU - Chen, Shih Ann

AU - Lin, Tin Kwang

AU - Wu, Mei Hwan

AU - Lo, Huey Ming

AU - Huang, Shoei K.Stephen

AU - Lin, Jiunn Lee

PY - 2005/9/1

Y1 - 2005/9/1

N2 - Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.

AB - Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.

KW - K-channel

KW - Long QT syndrome

KW - Na-channel

KW - Sudden death

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