Abstract
Restless legs syndrome (RLS) is a common neurological condition with three loci (12q, 14q, and 9p) described so far, although none of these genes has yet been identified. We report a genomewide linkage scan of patients with RLS (n = 37) assessed in a population isolate (n = 530) of South Tyrol (Italy). Using both nonparametric and parametric analyses, we initially obtained suggestive evidence of a novel locus on chromosome 2q, with nominal evidence of linkage on chromosomes 5p and 17p. Follow-up genotyping yielded significant evidence of linkage (nonparametric LOD score 5.5, P ≤ .0000033; heterogeneity LOD score 5.1; α = 1.0) on chromosome 2q. Three families (S01, S05, and S016) were shown to descend from a common founder couple. A disease haplotype shared between family S01 and family S05 defines a candidate region of 8.2 cM; in addition, the single affected individual in family S016 shares three linked alleles at neighboring markers, which suggests a reduced candidate interval of only 1.6 cM. Two-point linkage analysis in this 10-generation pedigree provided significant evidence of a novel RLS locus in this region (LOD score 4.1). These findings reemphasize the genetic heterogeneity of the disorder and strongly support the identification of a novel locus for RLS on chromosome 2q.
| Original language | English |
|---|---|
| Journal | American Journal of Human Genetics |
| Volume | 79 |
| Issue number | 4 |
| Pages (from-to) | 716-723 |
| Number of pages | 8 |
| ISSN | 0002-9297 |
| DOIs | |
| Publication status | Published - 01.01.2006 |
Funding
The authors are grateful to the study participants, the primary care physician of the village (Stocker Raffaela), and the Hospital of Silandro (Department of Laboratory Medicine), for their participation and collaboration in this research project. We thank Sara Pedrotti and Agatha Eisendle for technical support. We gratefully acknowledge P. Michael Conneally and Tatiana Foroud, for helpful comments on the manuscript. The study was supported by the Ministry of Health of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse Foundation (support to P.P.P.), the South Tyrolean Parkinson Disease Association (support to P.P.P.), and by the Volkswagen Foundation (support to C.K.).
