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

ABSTRACT

BACKGROUND: 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. OBJECTIVES: To describe the clinical characteristics of a large three-generation family with primary erythermalgia and to test for genetic linkage to chromosome 2q. METHODS: 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. RESULTS: 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. CONCLUSIONS: In this family with autosomal dominant primary erythermalgia, exclusion of linkage to chromosome 2q is strongly suggestive for genetic heterogeneity.