Primary erythermalgia as a sodium channelopathy: screening for SCN9A mutations: exclusion of a causal role of SCN10A and SCN11A.
OBJECTIVE
To elucidate the rate of missense mutations in the SCN9A gene (which encodes sodium channel Na(v)1.7) (OMIM 603415) among patients with primary erythermalgia and to examine the possibility that other sodium channels can cause the disease.


METHODS
Case series.


METHODS
Department of Medicine, Radboud University Nijmegen, the Netherlands.


METHODS
Six patients with sporadic and 9 with unique familial primary erythermalgia. Interventions Questionnaire to determine clinical profile and sequencing of all coding exons from SCN9A and those of SCN10A (OMIM 604427) and SCN11A (OMIM 604385) in 2 selected cases with a clear family history of the disease.


METHODS
Detection of SCN9A mutation.


RESULTS
We identified 1 patient with an SCN9A mutation. This mutation (I848T) has been associated with primary erythermalgia. Sequencing of 2 other candidate genes did not show mutations in 2 patients with familial primary erythermalgia.


CONCLUSIONS
The Na(v)1.7 voltage-gated sodium channels are related to syndromes of altered nociception. We detected a low SCN9A mutation rate in patients with primary erythermalgia, suggesting that pain syndromes in the skin may have a polygenic basis.
Drenth
Joost P H
JP
Division of Gastroenterology and Hepatology, Department of Medicine, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, the Netherlands. JoostPHDrenth@CS.com
Te Morsche
Rene H M
RH
Mansour
Sahar
S
Mortimer
Peter S
PS
D000293:Adolescent; D000328:Adult; D004247:DNA / Q000032:analysis; D004916:Erythromelalgia / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009426:Netherlands; D009479:Neuropeptides / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics*; D044465:White People / Q000235:genetics
D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C568317:SCN10A protein, human; C491886:SCN11A protein, human; C486866:SCN9A protein, human; D015222:Sodium Channels; D004247:DNA