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Fine-Mapping of Restless Legs Locus 4 (RLS4) Identifies a Haplotype over the SPATS2L and KCTD18 Genes

Abstract

Restless legs syndrome (RLS) is a sleep-related movement disorder that affects up to 15 % of the population. Linkage studies have identified several genomic loci in single families (12q, 14q, 9p, 2q, 20p and 16p, respectively). However, confirmation of these loci has not always been achieved, and causative mutations have not yet been identified. The locus on chromosome 2q33 (RLS4) was identified in two South Tyrolean families who shared a haplotype of microsatellite marker alleles across an 8.2-cM region. To pinpoint the gene localisation within RLS4, additional families from the same geographic region were evaluated, and linkage was replicated in one family. Within the candidate region, we initially found a haplotype of 23 single nucleotide polymorphism markers spanning 131.6 Kb shared by all affected members of the three linked families. Using a next generation sequencing approach, we further restricted the shared candidate region to 46.9 Kb over the potassium channel-related gene KCTD18 and exons 10-13 of SPATS2L.

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Acknowledgments

The authors are grateful to the study participants and the primary care physicians of the villages for their participation and collaboration in this research project. We thank Martin Gögele and Daniel Taliun for their technical support. The study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano and the South Tyrolean Sparkasse Foundation.

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Correspondence to Peter P. Pramstaller.

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Pichler, I., Schwienbacher, C., Zanon, A. et al. Fine-Mapping of Restless Legs Locus 4 (RLS4) Identifies a Haplotype over the SPATS2L and KCTD18 Genes. J Mol Neurosci 49, 600–605 (2013). https://doi.org/10.1007/s12031-012-9891-5

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  • DOI: https://doi.org/10.1007/s12031-012-9891-5

Keywords

  • Restless legs syndrome
  • Familial form
  • Genetics
  • Isolated population
  • RLS4