IR@PKUHSC  > 北京大学第一临床医学院  > 皮肤性病科
学科主题临床医学
Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off
Choi, Jin-Sung1,2,3; Zhang, Lili4; Dib-Hajj, Sulayman D.1,2,3; Han, Chongyang1,2,3,5,6; Tyrrell, Lynda1,2,3; Lin, Zhimiao4; Wang, Xiaoliang5,6; Yang, Yong1,2,3,4; Waxman, Stephen G.1,2,3
关键词Inherited neuropathy Channelopathy Pain Erythermalgia Sodium channel blockers Local anesthetics
刊名EXPERIMENTAL NEUROLOGY
2009-04-01
DOI10.1016/j.expneurol.2008.12.012
216期:2页:383-389
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]GATED SODIUM-CHANNELS ; EXTREME PAIN DISORDER ; HYPERKALEMIC PERIODIC PARALYSIS ; SEVERE MYOCLONIC EPILEPSY ; PRIMARY ERYTHERMALGIA ; SCN9A MUTATIONS ; ALPHA-SUBUNIT ; NEURONS ; INACTIVATION ; ACTIVATION
英文摘要

Inherited erythromelalgia (IEM), characterized by episodic burning pain and erythema of the extremities, is produced by gain-of-function mutations in sodium channel Na(v)1.7, which is preferentially expressed in nociceptive and sympathetic neurons. Most patients do not respond to pharmacotherapy, although occasional reports document patients as showing partial relief with lidocaine or mexiletine. A 7-year-old girl, with a two-year history of symmetric burning pain and erythema in her hands and feet, was diagnosed with erythromelalgia. Treatment with mexiletine reduced the number and severity of pain episodes. We report here a new IEM Na(v)1.7 Mutation in this patient, and its response to mexiletine. SCN9A exons from the proband were amplified and sequenced. We identified a single nucleotide substitution (T2616G) in exon 15, not present in 200 ethnically-matched control alleles, which substitutes valine 872 by glycine (V872G) within DII/S5. Whole-cell patch-clamp analysis of wild-type and mutant Na(v)1.7 channels in mammalian cells show that V872G shifts activation by -10 mV, slows deactivation, and generates larger ramp currents. We observed a stronger use-dependent fall-off in Current following exposure to mexiletine for V872G compared to wild-type channels. These observations Suggest that some patients with IEM may show a favorable response to mexiletine due to a use-dependent effect on mutant Nav1.7 channels. Continued relief from pain, even after mexiletine was discontinued in this patient, might suggest that early treatment may slow the progression of the disease. (c) 2008 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000264606600018
项目编号NCET-06-0015 ; 30400168
资助机构National Program for New Century Excellent Talents in University ; National Natural Science Foundation
引用统计
被引频次:54[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/68078
专题北京大学第一临床医学院_皮肤性病科
作者单位1.Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA
2.Yale Univ, Sch Med, Ctr Neurosci & Regenerat Res, New Haven, CT 06510 USA
3.VA Connecticut Healthcare Syst, Rehabil Res Ctr, West Haven, CT 06516 USA
4.Peking Univ, Hosp 1, Dept Dermatol, Beijing 100034, Peoples R China
5.Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China
6.Peking Union Med Coll, Beijing 100050, Peoples R China
推荐引用方式
GB/T 7714
Choi, Jin-Sung,Zhang, Lili,Dib-Hajj, Sulayman D.,et al. Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off[J]. EXPERIMENTAL NEUROLOGY,2009,216(2):383-389.
APA Choi, Jin-Sung.,Zhang, Lili.,Dib-Hajj, Sulayman D..,Han, Chongyang.,Tyrrell, Lynda.,...&Waxman, Stephen G..(2009).Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off.EXPERIMENTAL NEUROLOGY,216(2),383-389.
MLA Choi, Jin-Sung,et al."Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off".EXPERIMENTAL NEUROLOGY 216.2(2009):383-389.
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