Genetic heterogeneity and exclusion of a modifying locus at 2q in a family with autosomal dominant primary erythermalgia

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm and painful hands and/or feet. In a previous study we reported localization of a gene for primary erythermalgia to a 7.94-cM region on chromosome 2q. A recent study reported voltage-gated sodium channel gene SCN9a sequence variants in a family and a single individual with primary erythermalgia. To describe the clinical characteristics of a large three-generation family with primary erythermalgia and to test for genetic linkage to chromosome 2q. We collected clinical data of a 10-member three-generation family with autosomal dominant primary erythermalgia. In addition, we performed linkage analysis and searched for SCN9a variants using a restriction fragment length polymorphism assay. We established the diagnosis of autosomal dominant primary erythermalgia in six of 10 family members. We excluded linkage to chromosome 2q and could not detect SCN9A variants in this family. In this family with autosomal dominant primary erythermalgia, exclusion of linkage to chromosome 2q is strongly suggestive for genetic heterogeneity.