Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate

Irene Pichler, Fabio Marroni, Claudia Beu Volpato, James F. Gusella, Christine Klein, Giorgio Casari, Alessandro De Grandi, Peter P. Pramstaller

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)716-723
Number of pages8
JournalAmerican Journal of Human Genetics
Volume79
Issue number4
DOIs
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Genetics

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