Journal of Molecular Neuroscience

, Volume 49, Issue 3, pp 600–605

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

  • Irene Pichler
  • Christine Schwienbacher
  • Alessandra Zanon
  • Christian Fuchsberger
  • Alice Serafin
  • Maurizio F. Facheris
  • Fabio Marroni
  • Cristian Pattaro
  • Yiping Shen
  • Christian Tellgren-Roth
  • Ulf Gyllensten
  • James F. Gusella
  • Andrew A. Hicks
  • Peter P. Pramstaller
Article

DOI: 10.1007/s12031-012-9891-5

Cite this article as:
Pichler, I., Schwienbacher, C., Zanon, A. et al. J Mol Neurosci (2013) 49: 600. doi:10.1007/s12031-012-9891-5

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.

Keywords

Restless legs syndrome Familial form Genetics Isolated population RLS4 

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Irene Pichler
    • 1
  • Christine Schwienbacher
    • 1
    • 2
  • Alessandra Zanon
    • 1
  • Christian Fuchsberger
    • 3
  • Alice Serafin
    • 1
  • Maurizio F. Facheris
    • 1
  • Fabio Marroni
    • 4
  • Cristian Pattaro
    • 1
  • Yiping Shen
    • 5
    • 6
    • 7
    • 8
  • Christian Tellgren-Roth
    • 9
  • Ulf Gyllensten
    • 9
  • James F. Gusella
    • 5
    • 10
  • Andrew A. Hicks
    • 1
  • Peter P. Pramstaller
    • 1
    • 11
    • 12
  1. 1.Center for BiomedicineEuropean Academy Bozen/Bolzano (EURAC) (Affiliated institute of the University of Lübeck)Bozen/BolzanoItaly
  2. 2.Department of Experimental and Diagnostic MedicineUniversity of FerraraFerraraItaly
  3. 3.Center for Statistical GeneticsUniversity of MichiganAnn ArborUSA
  4. 4.Institute of Applied GenomicsUdineItaly
  5. 5.Molecular Neurogenetics Unit, Center for Human Genetic ResearchMassachusetts General HospitalBostonUSA
  6. 6.Department of Laboratory MedicineChildren’s Hospital BostonBostonUSA
  7. 7.Department of PathologyHarvard Medical SchoolBostonUSA
  8. 8.Shanghai Children’s Medical CenterShanghai Jiaotong University School of MedicineShanghaiChina
  9. 9.Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, SciLifeLab UppsalaUppsala UniversityUppsalaSweden
  10. 10.Department of GeneticsHarvard Medical SchoolBostonUSA
  11. 11.Department of NeurologyGeneral Central HospitalBolzanoItaly
  12. 12.Department of NeurologyUniversity of LübeckLübeckGermany

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