Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome

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Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome. / Yang, Yanzong; Yang, Yiqing; Liang, Bo; Liu, Jinqiu; Li, Jun; Grunnet, Morten; Olesen, Søren-Peter; Rasmussen, Hanne B; Ellinor, Patrick T; Gao, Lianjun; Lin, Xiaoping; Li, Li; Wang, Lei; Xiao, Junjie; Liu, Yi; Liu, Ying; Zhang, Shulong; Liang, Dandan; Peng, Luying; Jespersen, Thomas; Chen, Yi-Han.

In: American Journal of Human Genetics, Vol. 86, No. 6, 2010, p. 872-80.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Yang, Y, Yang, Y, Liang, B, Liu, J, Li, J, Grunnet, M, Olesen, S-P, Rasmussen, HB, Ellinor, PT, Gao, L, Lin, X, Li, L, Wang, L, Xiao, J, Liu, Y, Liu, Y, Zhang, S, Liang, D, Peng, L, Jespersen, T & Chen, Y-H 2010, 'Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome', American Journal of Human Genetics, vol. 86, no. 6, pp. 872-80. https://doi.org/10.1016/j.ajhg.2010.04.017

APA

Yang, Y., Yang, Y., Liang, B., Liu, J., Li, J., Grunnet, M., Olesen, S-P., Rasmussen, H. B., Ellinor, P. T., Gao, L., Lin, X., Li, L., Wang, L., Xiao, J., Liu, Y., Liu, Y., Zhang, S., Liang, D., Peng, L., ... Chen, Y-H. (2010). Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome. American Journal of Human Genetics, 86(6), 872-80. https://doi.org/10.1016/j.ajhg.2010.04.017

Vancouver

Yang Y, Yang Y, Liang B, Liu J, Li J, Grunnet M et al. Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome. American Journal of Human Genetics. 2010;86(6):872-80. https://doi.org/10.1016/j.ajhg.2010.04.017

Author

Yang, Yanzong ; Yang, Yiqing ; Liang, Bo ; Liu, Jinqiu ; Li, Jun ; Grunnet, Morten ; Olesen, Søren-Peter ; Rasmussen, Hanne B ; Ellinor, Patrick T ; Gao, Lianjun ; Lin, Xiaoping ; Li, Li ; Wang, Lei ; Xiao, Junjie ; Liu, Yi ; Liu, Ying ; Zhang, Shulong ; Liang, Dandan ; Peng, Luying ; Jespersen, Thomas ; Chen, Yi-Han. / Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome. In: American Journal of Human Genetics. 2010 ; Vol. 86, No. 6. pp. 872-80.

Bibtex

@article{6525f0a6ee1a46ea85ca8d55ce9e58be,

title = "Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome",

abstract = "Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS.",

keywords = "Adolescent, Adult, Aged, Aminophylline, Atropine, Chromosome Mapping, Drug Combinations, Female, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Genetic Linkage, Humans, Infant, Newborn, Long QT Syndrome, Male, Middle Aged, Mutation, Myocardium, Nitroglycerin, Papaverine, Pedigree, Phenobarbital",

author = "Yanzong Yang and Yiqing Yang and Bo Liang and Jinqiu Liu and Jun Li and Morten Grunnet and S{\o}ren-Peter Olesen and Rasmussen, {Hanne B} and Ellinor, {Patrick T} and Lianjun Gao and Xiaoping Lin and Li Li and Lei Wang and Junjie Xiao and Yi Liu and Ying Liu and Shulong Zhang and Dandan Liang and Luying Peng and Thomas Jespersen and Yi-Han Chen",

year = "2010",

doi = "10.1016/j.ajhg.2010.04.017",

language = "English",

volume = "86",

pages = "872--80",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

RIS

TY - JOUR

T1 - Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome

AU - Yang, Yanzong

AU - Yang, Yiqing

AU - Liang, Bo

AU - Liu, Jinqiu

AU - Li, Jun

AU - Grunnet, Morten

AU - Olesen, Søren-Peter

AU - Rasmussen, Hanne B

AU - Ellinor, Patrick T

AU - Gao, Lianjun

AU - Lin, Xiaoping

AU - Li, Li

AU - Wang, Lei

AU - Xiao, Junjie

AU - Liu, Yi

AU - Liu, Ying

AU - Zhang, Shulong

AU - Liang, Dandan

AU - Peng, Luying

AU - Jespersen, Thomas

AU - Chen, Yi-Han

PY - 2010

Y1 - 2010

N2 - Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS.

AB - Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aminophylline

KW - Atropine

KW - Chromosome Mapping

KW - Drug Combinations

KW - Female

KW - G Protein-Coupled Inwardly-Rectifying Potassium Channels

KW - Genetic Linkage

KW - Humans

KW - Infant, Newborn

KW - Long QT Syndrome

KW - Male

KW - Middle Aged

KW - Mutation

KW - Myocardium

KW - Nitroglycerin

KW - Papaverine

KW - Pedigree

KW - Phenobarbital

U2 - 10.1016/j.ajhg.2010.04.017

DO - 10.1016/j.ajhg.2010.04.017

M3 - Journal article

C2 - 20560207

VL - 86

SP - 872

EP - 880

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 6

ER -

ID: 33026695

Department of Biomedical Sciences