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Science 14 October 2005:
Vol. 310. no. 5746, pp. 317 - 320
DOI: 10.1126/science.1116502
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Reports

Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome

Jesse F. Abelson,1,2* Kenneth Y. Kwan,3,4* Brian J. O'Roak,2* Danielle Y. Baek,1,2 Althea A. Stillman,2 Thomas M. Morgan,2 Carol A. Mathews,8 David L. Pauls,9 Mladen-Roko Rasin,3 Murat Gunel,5 Nicole R. Davis,1,2 A. Gulhan Ercan-Sencicek,1,2 Danielle H. Guez,2 John A. Spertus,10 James F. Leckman,1 Leon S. Dure, IV,11 Roger Kurlan,12 Harvey S. Singer,13 Donald L. Gilbert,14 Anita Farhi,7 Angeliki Louvi,5 Richard P. Lifton,2,6,7 Nenad Sestan,3,4 Matthew W. State1,2,4,6{dagger}

Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS.

1 Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
2 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
3 Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
4 Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520, USA.
5 Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
6 Center for Human Genetics and Genomics, Yale University School of Medicine, New Haven, CT 06520, USA.
7 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
8 Department of Psychiatry, University of California–San Diego, San Diego, CA 92093, USA.
9 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
10 Department of Medicine, University of Missouri–Kansas City, Kansas City, MO 64111, USA.
11 Division of Pediatric Neurology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
12 Department of Neurology, University of Rochester School of Medicine, Rochester, NY 14642, USA.
13 Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
14 Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: matthew.state{at}yale.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)