Evidence for genetic heterogeneity in Restless Legs Syndrome

40–60% of Restless Legs Syndrome (RLS,OMIM102300) patients report a positive family history. Two major susceptibility loci for RLS have been published. In a French Canadian family, linkage was shown to chromosome 12q12-q21 assuming an recessive- and in an Italian family on chromosome 14q13-q21 assuming an autosomal-dominant mode of inheritance. We report a Bavarian family (113 individuals,32 RLS-affecteds). Genotyping of the RLS loci on 12q and 14q was performed in 46 family members using 18 (12q:11;14q:7) microsatellite markers. PCRs were performed with fluorescent dye labeled universal primer and microsatellite specific primers with a universal sequence tag at the 5’end. Linkage analysis was performed with different mode of inheritance models, including the recessive and autosomal dominant model. Two-point and non-parametric multipoint LOD scores, excluded linkage of our family to the 12q and 14q loci. This indicates further genetic heterogeneity of RLS with a locus outside the two published susceptibility regions.