The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32

Abstract

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders.

Figure 1

Pedigree of five families (A, family 1; B, family 2; C, family 3; D, family 4; E, family 5, with autosomal dominant–inherited primary erythermalgia. Females are indicated by circles and males by squares. Blackened figures denote affected individuals, and figures with slashes denote deceased individuals. Genotypes for chromosome 2 markers were determined for all living persons shown. Haplotypes for boxed portions of the pedigree are presented.

Figure 2

Multilocus analysis, with the primary erythermalgia gene, against a fixed genetic map of linked markers for family 1. Order of markers and distances are taken from published sources (Dib et al. 1996). The highest probability for location of the primary erythermalgia gene is in the region between D2S1353 and D2S1391.