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Replication of association between a SLITRK1 haplotype and Tourette Syndrome in a large sample of families

Molecular Psychiatry volume 17, pages 665–668 (2012)Cite this article

Tourette Syndrome (TS) is a neuropsychiatric disorder of complex etiological background, with multiple genes interacting with environmental factors to lead to the onset of symptoms. Although multiple genetic loci have been implicated in TS etiology, to date, no single chromosomal region has been consistently replicated as a TS susceptibility region.1 The implication of a member of the SLIT and TRK family of proteins (SLITRK1) in TS etiology2 has spurred intense debate, with the significance of the original findings being questioned, and multiple studies suggesting that, if this gene is indeed involved in TS etiology, it may only account for a very small fraction of cases. Here, studying one of the largest family samples that have been analyzed for TS to date, we further investigate the contribution of SLITRK1 in TS risk, and show significant over-transmission of alleles and haplotypes to affected individuals, by a rate of about 1.5.

SLITRK1 is a type-I transmembrane protein with an extracellular leucine-rich repeat domain homologous to SLIT and a short intracellular domain lacking the tyrosine phosphorylation motifs that are found among the other members of SLITRK family.3 It has been shown to control neurite outgrowth and it is expressed in the embryonic and postnatal brain, including the cortex, thalamus and the basal ganglia, reflecting the neuroanatomical regions most commonly implicated in TS.4 By studying mouse, monkey and human brains, Stillman et al.5 recently showed that SLITRK1 expression in the striatum is high during early brain development but significantly diminished later. This suggests a possible role of SLITRK1 in establishing the corticostriatal circuitry, in concordance with the neurodevelopmental hypothesis for TS etiology. Furthermore, it has been demonstrated that SLITRK1 interacts with 14-3-3 proteins, which are ubiquitously expressed phosphorylation-binding proteins that regulate several important cellular processes, including cell proliferation, neuronal migration and membrane excitability.6

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Acknowledgements

This study was supported by Tourette Syndrome Association, USA and COST Action BM0905.

Author information

Author notes

  1. The Tourette Syndrome Genetics-Southern and Eastern Europe Initiative Consortium.

  2. See Supplementary Appendix for full list of members of TSGeneSEE consortium.

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupoli, Greece

    I Karagiannidis, G Panteloglou & P Paschou

  2. Department of Materno-Infantile and Radiological Science, University of Catania, Catania, Italy

    R Rizzo

  3. Vadaskert Clinic for Child and Adolescent Psychiatry, Budapest, Hungary

    Z Tarnok, L Farkas & P Nagy

  4. Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland

    T Wolanczyk & U Szymanska

  5. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany

    J Hebebrand

  6. Institute for Human Genetics, University of Bonn, Bonn, Germany

    M M Nöthen

  7. Department of Child and Adolescent Psychiatry,

    G Lehmkuhl

  8. University of Cologne, Cologne, Germany

    G Lehmkuhl

  9. Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, University of Semmelweis, Budapest, Hungary

    C Barta

  10. Department of Pharmacology,

    D M Miranda

  11. Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    D M Miranda

  12. Toronto Western Research Institute, University Health Network, Toronto, ON, Canada

    Y Feng, P Sandor & C Barr

  13. Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada

    C Barr

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  1. I Karagiannidis
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  2. R Rizzo
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  8. L Farkas
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  9. P Nagy
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TSGeneSEE

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Correspondence to P Paschou.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Karagiannidis, I., Rizzo, R., Tarnok, Z. et al. Replication of association between a SLITRK1 haplotype and Tourette Syndrome in a large sample of families. Mol Psychiatry 17, 665–668 (2012). https://doi.org/10.1038/mp.2011.151

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