Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.(Short Report)

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.

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J Med Genet 2004;41:171-174. doi: 10.1136/jmg.2003.012153

Primary erythermalgia (MIM 133020) is a rare disorder characterised by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. (1) In patients, standing, exercise, or local exposure to heat can induce the symptoms, and keeping the involved extremities at an icy cold temperature is the most effective way to relieve pain. Symptoms of primary erythermalgia arise in childhood or adolescence; with age, the symptoms may progress and become constant. Histopathological examination reveals a reduced density of skin autonomic nerve plexuses. (2) Many therapeutic options have been tested with variable alleviatory results. (3) this disorder may be inherited as an autosomal dominant trait. (4-6) A previous study (7) established the linkage of primary erythermalgia to a 7.94 cM interval on chromosome 2q. We report here the linkage of primary erythermalgia in a Chinese family to …