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

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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

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Restless Legs Syndrome
Chromosomes
Population
Inborn Genetic Diseases
Genetic Heterogeneity
Pedigree
Haplotypes
Italy
Alleles
Genes

ASJC Scopus subject areas

  • Genetics

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Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate. / Pichler, Irene; Marroni, Fabio; Volpato, Claudia Beu; Gusella, James F.; Klein, Christine; Casari, Giorgio; De Grandi, Alessandro; Pramstaller, Peter P.

In: American Journal of Human Genetics, Vol. 79, No. 4, 10.2006, p. 716-723.

Research output: Contribution to journalArticle

Pichler, Irene ; Marroni, Fabio ; Volpato, Claudia Beu ; Gusella, James F. ; Klein, Christine ; Casari, Giorgio ; De Grandi, Alessandro ; Pramstaller, Peter P. / Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate. In: American Journal of Human Genetics. 2006 ; Vol. 79, No. 4. pp. 716-723.
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