title: Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate.
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<or=.0000033; heterogeneity LOD score 5.1; alpha =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.
authors.affiliation: Institute of Genetic Medicine, European Academy, Bolzano, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Pichler
authors.forename: Fabio
authors.initials: F
authors.lastname: Marroni
authors.forename: Claudia Beu
authors.initials: CB
authors.lastname: Volpato
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Giorgio
authors.initials: G
authors.lastname: Casari
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Grandi
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D012148:Restless Legs Syndrome / Q000235:genetics*