Gain-of-Function Mutations in SCN11A Cause Familial Episodic Pain

doi:10.1016/j.ajhg.2013.09.016

CORC > 北京大学 > 生命科学学院

	Gain-of-Function Mutations in SCN11A Cause Familial Episodic Pain
	Zhang, Xiang Yang ; Wen, Jingmin ; Yang, Wei ; Wang, Cheng ; Gao, Luna ; Zheng, Liang Hong ; Wang, Tao ; Ran, Kaikai ; Li, Yulei ; Li, Xiangyang ; Xu, Ming ; Luo, Junyu ; Feng, Shenglei ; Ma, Xixiang ; Ma, Hongying ; Chai, Zuying ; Zhou, Zhuan ; Yao, Jing ; Zhang, Xue ; Liu, Jing Yu
刊名	american journal of human genetics
	2013
关键词	SODIUM-CHANNEL NA(V)1.7 SPINAL SENSORY NEURONS RESISTANT NA+ CURRENT SCN9A EXCITABILITY ACTIVATION EXPRESSION NEUROPATHY DISORDERS THRESHOLD
DOI	10.1016/j.ajhg.2013.09.016
英文摘要	Many ion channel genes have been associated with human genetic pain disorders. Here we report two large Chinese families with autosomal-dominant episodic pain. We performed a genome-wide linkage scan with microsatellite markers after excluding mutations in three known genes (SCN9A, SCN10A, and TRPA1) that cause similar pain syndrome to our findings, and we mapped the genetic locus to a 7.81 Mb region on chromosome 3p22.3-p21.32. By using whole-exome sequencing followed by conventional Sanger sequencing, we identified two missense mutations in the gene encoding voltage-gated sodium channel Na(v)1.9 (SCN11A): c.673C>T (p.Arg225Cys) and c.2423C>G (p.Ala808Gly) (one in each family). Each mutation showed a perfect cosegregation with the pain phenotype in the corresponding family, and neither of them was detected in 1,021 normal individuals. Both missense mutations were predicted to change a highly conserved amino acid residue of the human Na(v)1.9 channel. We expressed the two SCN11A mutants in mouse dorsal root ganglion (DRG) neurons and showed that both mutations enhanced the channel's electrical activities and induced hyperexcitablity of DRG neurons. Taken together, our results suggest that gain-of-function mutations in SCN11A can be causative of an autosomal-dominant episodic pain disorder.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000326996600016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Genetics & Heredity; SCI(E); 51; ARTICLE; 5; 957-966; 93
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/220138]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhang, Xiang Yang,Wen, Jingmin,Yang, Wei,et al. Gain-of-Function Mutations in SCN11A Cause Familial Episodic Pain[J]. american journal of human genetics,2013.
APA	Zhang, Xiang Yang.,Wen, Jingmin.,Yang, Wei.,Wang, Cheng.,Gao, Luna.,...&Liu, Jing Yu.(2013).Gain-of-Function Mutations in SCN11A Cause Familial Episodic Pain.american journal of human genetics.
MLA	Zhang, Xiang Yang,et al."Gain-of-Function Mutations in SCN11A Cause Familial Episodic Pain".american journal of human genetics (2013).