Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

被引：74

作者：

Andres-Enguix, Isabelle ^{[3
]}

Shang, Lijun ^{[3
]}

Stansfeld, Phillip J. ^{[4
]}

Morahan, Julia M. ^{[5
]}

Sansom, Mark S. P. ^{[4
,9
]}

Lafreniere, Ronald G. ^{[6
,7
]}

Roy, Bishakha ^{[8
]}

Griffiths, Lyn R. ^{[8
]}

Rouleau, Guy A. ^{[6
,7
]}

Ebers, George C. ^{[5
]}

Cader, Zameel M. ^{[1
,2
]}

Tucker, Stephen J. ^{[3
,9
]}

机构：

[1] Univ Oxford, Funct Genom Unit, Dept Physiol Anat & Genet, Oxford, England

[2] John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England

[3] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England

[4] Univ Oxford, Dept Biochem, Struct Bioinformat & Computat Biochem Unit, Oxford OX1 3QU, England

[5] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[6] Univ Montreal, Ctr Excellence Neurosci, Montreal, PQ H3C 3J7, Canada

[7] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada

[8] Griffith Univ, Genom Res Ctr, Griffith Inst Hlth & Med Res, Nathan, Qld 4111, Australia

[9] Univ Oxford, OXION Ion Channel Initiat, Oxford, England

来源：

SCIENTIFIC REPORTS | 2012年 / 2卷

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

CORTICAL SPREADING DEPRESSION; FAMILIAL HEMIPLEGIC MIGRAINE; GENOME-WIDE ASSOCIATION; POTASSIUM CHANNEL; MUTATIONS; EXPRESSION; NEUROBIOLOGY; MECHANISM; ALTER; CA2+;

D O I：

10.1038/srep00237

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder.

引用

页数：7

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