Sequence variants in SLITRK1 are associated with Tourette's syndrome.
paper
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- Authors
- Abelson, Jesse F; Kwan, Kenneth Y; O'Roak, Brian J; Baek, Danielle Y; Stillman, Althea A; Morgan, Thomas M; Mathews, Carol A; Pauls, David L; Rasin, Mladen-Roko; Gunel, Murat; Davis, Nicole R; Ercan-Sencicek, A Gulhan; Guez, Danielle H; Spertus, John A; Leckman, James F; Dure, Leon S; Kurlan, Roger; Singer, Harvey S; Gilbert, Donald L; Farhi, Anita; Louvi, Angeliki; Lifton, Richard P; Sestan, Nenad; State, Matthew W
- Year
- 2005
- Journal
- Science (New York, N.Y.)
- PMID
- 16224024
- DOI
- 10.1126/science.1116502
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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