Cytogenetic location: 2q33 Genomic coordinates (GRCh38): 2:196,600,001-208,200,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2q33 | {Restless legs syndrome 4} | 610439 | 2 |
Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003).
For additional information and a discussion of genetic heterogeneity of restless legs syndrome, see RLS1 (102300).
Pichler et al. (2006) reported a genomewide linkage analysis of patients with RLS collected from 1 small village that had conserved a high degree of isolation in the Western Alps of South Tyrol (Italy). The population showed increased background linkage disequilibrium (LD) due to the peculiar demographic history that had led to genetic drift and founder effect. Historical documents allowed the reconstruction of extended pedigrees as far back as the 17th century. Using both nonparametric and parametric analyses, Pichler et al. (2006) initially obtained suggestive evidence for a novel locus on chromosome 2q. Follow-up genotyping yielded significant evidence of linkage (nonparametric lod score 5.5, p less than or equal to 0.0000033) between markers D2S311 and D2S317 (11.7 cM). Genotypic data for 20 markers on chromosome 2q were used to examine the pattern of haplotype transmission in all individuals in the 18 families analyzed, in an attempt to identify haplotype sharing among the 37 idiopathic RLS cases. They found that a common 7-marker haplotype in the chromosome 2q33 region was shared identical by descent by all 15 affected members of 3 families. From genealogic studies, they found that these 3 families descended from a common founder couple 10 generations ago. Two-point linkage analysis of this large genealogy resulted in a maximum lod score of 4.1 at theta = 0.0 at marker D2S2242. The remaining 15 families did not descend from a common ancestor; in those families, no common haplotype was observed, and the maximum lod score was 0.4 in 1 family.
Bonati, M. T., Ferini-Strambi, L., Aridon, P., Oldani, A., Zucconi, M., Casari, G. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain 126: 1485-1492, 2003. [PubMed: 12764067] [Full Text: https://doi.org/10.1093/brain/awg137]
Pichler, I., Marroni, F., Volpato, C. B., Gusella, J. F., Klein, C., Casari, G., De Grandi, A., Pramstaller, P. P. Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate. Am. J. Hum. Genet. 79: 716-723, 2006. [PubMed: 16960808] [Full Text: https://doi.org/10.1086/507875]