Medicine: Sequence variants in SLITRK1 are associated with Tourette's syndrome

Jesse F. Abelson, Kenneth Y. Kwan, Brian J. O'Roak, Danielle Y. Baek, Althea A. Stillman, Thomas M. Morgan, Carol A. Mathews, David L. Pauls, Mladen Roko Rašin, Murat Gunel, Nicole R. Davis, A. Gulhan Ercan-Sencicek, Danielle H. Guez, John A. Spertus, James F. Leckman, Leon S. Dure IV, Roger Kurlan, Harvey S. Singer, Donald L. Gilbert, Anita FarhiAngeliki Louvi, Richard P. Lifton, Nenad Šestan, Matthew W. State

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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.

Original languageEnglish (US)
Pages (from-to)317-320
Number of pages4
JournalScience
Volume310
Issue number5746
DOIs
StatePublished - Oct 14 2005

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ASJC Scopus subject areas

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Abelson, J. F., Kwan, K. Y., O'Roak, B. J., Baek, D. Y., Stillman, A. A., Morgan, T. M., Mathews, C. A., Pauls, D. L., Rašin, M. R., Gunel, M., Davis, N. R., Ercan-Sencicek, A. G., Guez, D. H., Spertus, J. A., Leckman, J. F., Dure IV, L. S., Kurlan, R., Singer, H. S., Gilbert, D. L., ... State, M. W. (2005). Medicine: Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science, 310(5746), 317-320. https://doi.org/10.1126/science.1116502