Full Text:   <3238>

CLC number: R541.7; R596.2

On-line Access: 

Received: 2004-10-15

Revision Accepted: 2004-12-26

Crosschecked: 0000-00-00

Cited: 4

Clicked: 7838

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2005 Vol.6 No.7 P.626-630


A novel splice mutation of HERG in a Chinese family with long QT syndrome

Author(s):  SHANG Yun-peng, XIE Xu-dong, WANG Xing-xiang, CHEN Jun-zhu, ZHU Jian-hua, TAO Qian-min, ZHENG Liang-rong

Affiliation(s):  Department of Cardiovascular Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

Corresponding email(s):   chenjunz@zju.edu.cn

Key Words:  HERG gene, Long QT syndrome, Cardiac arrhythmia, C-terminus, Acceptor splice site mutation

SHANG Yun-peng, XIE Xu-dong, WANG Xing-xiang, CHEN Jun-zhu, ZHU Jian-hua, TAO Qian-min, ZHENG Liang-rong. A novel splice mutation of HERG in a Chinese family with long QT syndrome[J]. Journal of Zhejiang University Science B, 2005, 6(7): 626-630.

@article{title="A novel splice mutation of HERG in a Chinese family with long QT syndrome",
author="SHANG Yun-peng, XIE Xu-dong, WANG Xing-xiang, CHEN Jun-zhu, ZHU Jian-hua, TAO Qian-min, ZHENG Liang-rong",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T A novel splice mutation of HERG in a Chinese family with long QT syndrome
%A SHANG Yun-peng
%A XIE Xu-dong
%A WANG Xing-xiang
%A CHEN Jun-zhu
%A ZHU Jian-hua
%A TAO Qian-min
%A ZHENG Liang-rong
%J Journal of Zhejiang University SCIENCE B
%V 6
%N 7
%P 626-630
%@ 1673-1581
%D 2005
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2005.B0626

T1 - A novel splice mutation of HERG in a Chinese family with long QT syndrome
A1 - SHANG Yun-peng
A1 - XIE Xu-dong
A1 - WANG Xing-xiang
A1 - CHEN Jun-zhu
A1 - ZHU Jian-hua
A1 - TAO Qian-min
A1 - ZHENG Liang-rong
J0 - Journal of Zhejiang University Science B
VL - 6
IS - 7
SP - 626
EP - 630
%@ 1673-1581
Y1 - 2005
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2005.B0626

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in c-terminus of HERG was identified in this Chinese LQTS family, leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (−12→−2)]. The mutation might affect, through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Berthet, M., Denjoy, I., Donger, C., Demay, L., Hammoude, H., Klug, D., Schulze-Bahr, E., Richard, P., Funke, H., Schwartz, K., et al., 1999. C-terminal HERG mutations: The role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence. Circulation, 99(11):1464-1470.

[2] Chen, J., Zou, A., Splawski, I., Keating, M.T., Sanguinetti, M.C., 1999. Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation. J Biol Chem, 274(15):10113-10118.

[3] Cui, J., Kagan, A., Qin, D., Mathew, J., Melman, Y.F., McDonald, T.V., 2001. Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2. J Biol Chem, 276(20):17244-17251.

[4] Curran, M.E., Splawski, I., Timothy, K.W., Vincent, G.M., Green, E.D., Keating, M.T., 1995. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell, 80(5):795-803.

[5] Johnson, W.H.Jr., Yang, P., Yang, T., Lau, Y.R., Mostella, B.A., Wolff, D.J., Roden, D.M., Benson, D.W., 2003. Clinical, genetic, and biophysical characterization of a homozygous HERG mutation causing severe neonatal long QT syndrome. Pediatr Res, 53(5):744-748.

[6] Keating, M.T., Sanguinetti, M.C., 2001. Molecular and cellular mechanisms of cardiac arrhythmias. Cell, 104(4):569-580.

[7] Krawczak, M., Reiss, J., Cooper, D.N., 1992. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: Causes and consequences. Hum Genet, 90(1-2):41-54.

[8] Lees-Miller, J.P., Duan, Y., Teng, G.Q., Thorstad, K., Duff, H.J., 2000. Novel gain-of-function mechanism in K(+) channel-related long-QT syndrome: Altered gating and selectivity in the HERG1 N629D mutant. Circ Res, 86(5):507-513.

[9] Nakajima, T., Furukawa, T., Hirano, Y., Tanaka, T., Sakurada, H., Takahashi, T., Nagai, R., Itoh, T., Katayama, Y., Nakamura, Y., et al., 1999. Voltage-shift of the current activation in HERG S4 mutation (R534C) in LQT2. Cardiovasc Res, 44(2):283-293.

[10] Neyroud, N., Tesson, F., Denjoy, I., Leibovici, M., Donger, C., Barhanin, J., Faure, S., Gary, F., Coumel, P., Petit, C., et al., 1997. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet, 15(2):186-189.

[11] Plaster, N.M., Tawil, R., Tristani-Firouzi, M., Canun, S., Bendahhou, S., Tsunoda, A., Donaldson, M.R., Iannaccone, S.T., Brunt, E., Barohn, R., et al., 2001. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen’s syndrome. Cell, 105(4):511-519.

[12] Priori, S.G., Barhanin, J., Hauer, R.N., Haverkamp, W., Jongsma, H.J., Kleber, A.G., McKenna, W.J., Roden, D.M., Rudy, Y., Schwartz, K., et al., 1999a. Genetic and molecular basis of cardiac arrhythmias: Impact on clinical management parts I and II. Circulation, 99(5):518-528.

[13] Priori, S.G., Napolitano, C., Schwartz, P.J., 1999b. Low penetrance in the long-QT syndrome: Clinical impact. Circulation, 99(4):529-533.

[14] Reese, M.G., Eeckman, F.H., Kulp, D., Haussler, D., 1997. Improved splice site detection in genie. J Comput Biol, 4(3):311-323.

[15] Roden, D.M., Spooner, P.M., 1999. Inherited long QT syndromes: A paradigm for understanding arrhythmogenesis. J Cardiovasc Electrophysiol, 10(12):1664-1683.

[16] Sanguinetti, M.C., Curran, M.E., Spector, P.S., Keating, M.T., 1996. Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia. Proc Natl Acad Sci USA, 93(5):2208-2212.

[17] Schwartz, P.J., Moss, A.J., Vincent, G.M., Crampton, R.S., 1993. Diagnostic criteria for the long QT syndrome. Circulation, 88(2):782-784.

[18] Splawski, I., Shen, J., Timothy, K.W., Vincent, G.M., Lehmann, M.H., Keating, M.T., 1998. Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics, 51(1):86-97.

[19] Splawski, I., Shen, J., Timothy, K.W., Lehmann, M.H., Priori, S., Robinson, J.L., Moss, A.J., Schwartz, P.J., Towbin, J.A., Vincent, G.M., et al., 2000. Spectrum of mutations in long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation, 102(10):1178-1185.

[20] Wainger, B.J., DeGennaro, M., Santoro, B., Siegelbaum, S.A., Tibbs, G.R., 2001. Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature, 411(6839):805-810.

[21] Wang, Q., Li, Z., Shen, J., Keating, M.T., 1996. Genomic organization of the human SCN5A gene encoding the cardiac sodium channel. Genomics, 34(1):9-16.

[22] Warmke, J.W., Ganetzky, B., 1994. A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci USA, 91(8):3438-3442.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE