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IR@PKUHSC  > 北京大学第一临床医学院  > 皮肤性病科  > 期刊论文
学科主题: 临床医学
题名:
Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off
作者: 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
发表日期: 2009-04-01
DOI: 10.1016/j.expneurol.2008.12.012
卷: 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
所属项目编号: NCET-06-0015 ; 30400168
项目资助者: National Program for New Century Excellent Talents in University ; National Natural Science Foundation
WOS记录号: WOS:000264606600018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68078
Appears in Collections:北京大学第一临床医学院_皮肤性病科_期刊论文

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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

Recommended Citation:
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.
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