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Neuroreceptor subunit genes and the genetic susceptibility to gilles de la tourette syndrome

  • Peter M. Brett
    Correspondence
    Address reprint requests to Dr. Peter M. Brett, Coeliac Research, The Rayne Institute. St. Thomas Hospital, Lambeth Palace Road, London SEI 7EH, United Kingdom.
    Affiliations
    Molecular Psychiatry Laboratory, Academic Department of Psychiatry, University College London Medical School, London, United Kingdom
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  • David Curtis
    Affiliations
    Molecular Psychiatry Laboratory, Academic Department of Psychiatry, University College London Medical School, London, United Kingdom
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  • Mary M. Robertson
    Affiliations
    Molecular Psychiatry Laboratory, Academic Department of Psychiatry, University College London Medical School, London, United Kingdom
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  • Hugh M.D. Gurling
    Affiliations
    Molecular Psychiatry Laboratory, Academic Department of Psychiatry, University College London Medical School, London, United Kingdom
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      Segregation studies have shown that Gilles de la Tourette Syndrome (GTS) is probably transmitted as an autosomal dominant gene disorder and can therefore be studied by classical linkage analysis to identify susceptibility loci. Many neurotransmitter systems have been implicated in the etiology of GTS. Most recently the alpha-1 subunit of the glycine receptor etiologically responsible for hyperekplexia has been hypothesized as the cause of the susceptibility to GTS. Because of this and the high concentration of other neuroreceptor genes at 5q33–35, it was decided to study this region and the associated gene cluster on chromosome 4p12–16 in a large British kindred multiply affected with GTS and chronic motor tics. The genotypes of the microsatellite markers at these loci were determined by polymerase chain reaction. The allele data were analyzed using both parametric and nonparametric methods. Approximate multipoint maps were constructed across the regions of interest using FASTLINK. All of the lod scores produced were negative, showing no evidence of linkage to GTS in the family studied. The multipoint maps showed good exclusion across these regions. The glycine receptor gene responsible for hyperekplexia and the other neuroreceptor genes examined in this paper are not involved in the etiology of GTS in this large pedigree.

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