title: SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels.
abstract: Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm and painful hands, and/or feet. We previously localized the gene for primary erythermalgia to a 7.94 cM region on chromosome 2q. Recently, Yang et al identified two missense mutations of the sodium channel alpha subunit SCN9A in patients with erythermalgia. The presence of voltage-gated sodium channels in sensory neurons is thought to play a crucial role in several chronic painful neuropathies. We examined four different families and two sporadic cases and detected missense sequence variants in SCN9A to be present in primary erythermalgia patients. A total of five of six mutations were located in highly conserved regions. One family with autosomal dominantly inherited erythermalgia was double heterozygous for two separate SCN9A mutations. These data establish primary erythermalgia as a neuropathic disorder and offers hope for treatment of this incapacitating painful disorder.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. joostphdrenth@cs.com
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: Rene H M
authors.initials: RH
authors.lastname: te Morsche
authors.forename: Gerard
authors.initials: G
authors.lastname: Guillet
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.forename: R Lee
authors.initials: RL
authors.lastname: Kirby
authors.forename: Jan B M J
authors.initials: JB
authors.lastname: Jansen
mesh_terms: D000328:Adult; D000409:Alanine; D017124:Conserved Sequence; D003545:Cysteine; D004916:Erythromelalgia / Q000235:genetics* / Q000473:pathology; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009422:Nervous System Diseases / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D015222:Sodium Channels / Q000235:genetics*; D013912:Threonine
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D015222:Sodium Channels; D013912:Threonine; D003545:Cysteine; D000409:Alanine