SHORT REPORT

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia

Y Yang^1,*, Y Wang^1,*, S Li^1,*, Z Xu², H Li³, L Ma², J Fan³, D Bu¹, B Liu⁴, Z Fan⁴, G Wu⁴, J Jin¹, B Ding¹, X Zhu¹, Y Shen⁴

¹ Department of Dermatology, Peking University First Hospital, Beijing, China
² Department of Dermatology, Beijing Children’s Hospital affiliated to the Capital University of Medical Sciences, Beijing, China
³ Department of Dermatology, General Hospital of PLA, Beijing, China
⁴ Chinese National Human Genome Centre, Beijing, China

Correspondence to:
Correspondence to:
Dr X Zhu
Department of Dermatology, Peking University First Hospital, No 8 Xishiku Street, Xicheng District, Beijing 100034, China; xjzhu{at}public.bta.net.cn
Correspondence to:
Dr Y Shen
Chinese National Human Genome Centre, No 3 Yongchangbeilu, Beijing 100176, China; sheny{at}ms.imicams.ac.cn

Primary erythermalgia is a rare autosomal dominant disease characterised by intermittent burning pain with redness and heat in the extremities. A previous study established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q, but the causative gene was not identified. We performed linkage analysis in a Chinese family with primary erythermalgia, and screened the mutations in the two candidate genes, SCN9A and GCA, in the family and a sporadic patient. Linkage analysis yielded a maximum lod score of 2.11 for both markers D2S2370 and D2S2330. Based on critical recombination events in two patients in the family, we further limited the genetic region to 5.98 cM between D2S2370 and D2S2345. We then identified two missense mutations in SCN9A in the family (T2573A) and the sporadic patient (T2543C). Our data suggest that mutations in SCN9A cause primary erythermalgia. SCN9A, encoding a voltage-gated sodium channel alpha subunit predominantly expressed in sensory and sympathetic neurones, may play an important role in nociception and vasomotor regulation.

Keywords: mutation; pain; primary erythermalgia; SCN9A; sodium channel

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