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

• Published in: British journal of dermatology (1951) Vol. 153; no. 1; pp. 174 - 177
• Main Authors: Burns, T.M., Te Morsche, R.H.M., Jansen, J.B.M.J., H. Drenth, J.P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2005; Blackwell; Oxford University Press
• Subjects: Adult; Biological and medical sciences; Chromosomes, Human, Pair 2 - genetics; Dermatology; Erythromelalgia - genetics; Erythromelalgia - pathology; Female; Genes, Dominant; Genetic Heterogeneity; Genetic Linkage; haplotype; heterogeneity; Humans; linkage; Lod Score; Male; Medical sciences; Middle Aged; mutation; NAV1.7 Voltage-Gated Sodium Channel; Pedigree; Phenotype; Polymorphism, Restriction Fragment Length; primary erythermalgia; Sodium Channels - genetics; Vascular disorders of the skin; Human; Acrosyndrome; Skin disease; primary crythermalgia; Dermatology; Family study; Cardiovascular disease; Genetic diversity; linkage; Vascular disease; Heterogeneity; Autosomal character; Genetic linkage; Primary; Capillary vessel disease; Genetics; Erythromelalgia; Mutation; Locus; Haplotype
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2005.06441.x

Summary 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.