2. Academic Validation
  3. Sequence variants in SLITRK1 are associated with Tourette's syndrome

Sequence variants in SLITRK1 are associated with Tourette's syndrome

  • Science. 2005 Oct 14;310(5746):317-20. doi: 10.1126/science.1116502.
Jesse F Abelson 1,  Kenneth Y Kwan,  Brian J O'Roak,  Danielle Y Baek,  Althea A Stillman,  Thomas M Morgan,  Carol A Mathews,  David L Pauls,  Mladen-Roko Rasin,  Murat Gunel,  Nicole R Davis,  A Gulhan Ercan-Sencicek,  Danielle H Guez,  John A Spertus,  James F Leckman,  Leon S Dure 4th,  Roger Kurlan,  Harvey S Singer,  Donald L Gilbert,  Anita Farhi,  Angeliki Louvi,  Richard P Lifton,  Nenad Sestan,  Matthew W State
Affiliations

Affiliation

  • 1 Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
PMID: 16224024 DOI: 10.1126/science.1116502
Abstract

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.

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