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

Jesse F. Abelson, Kenneth Y. Kwan, Brian 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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Tourette Syndrome
Medicine
Chromosomes
Frameshift Mutation
MicroRNAs
Binding Sites
Messenger RNA
Brain
Growth
Genes

ASJC Scopus subject areas

  • General

Cite this

Abelson, J. F., Kwan, K. Y., O'Roak, B., Baek, D. Y., Stillman, A. A., Morgan, T. M., ... 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

Medicine : Sequence variants in SLITRK1 are associated with Tourette's syndrome. / Abelson, Jesse F.; Kwan, Kenneth Y.; O'Roak, Brian; Baek, Danielle Y.; Stillman, Althea A.; Morgan, Thomas M.; Mathews, Carol A.; Pauls, David L.; Rašin, Mladen Roko; Gunel, Murat; Davis, Nicole R.; Ercan-Sencicek, A. Gulhan; Guez, Danielle H.; Spertus, John A.; Leckman, James F.; Dure IV, Leon S.; Kurlan, Roger; Singer, Harvey S.; Gilbert, Donald L.; Farhi, Anita; Louvi, Angeliki; Lifton, Richard P.; Šestan, Nenad; State, Matthew W.

In: Science, Vol. 310, No. 5746, 14.10.2005, p. 317-320.

Research output: Contribution to journalArticle

Abelson, JF, Kwan, KY, O'Roak, B, Baek, DY, Stillman, AA, Morgan, TM, Mathews, CA, Pauls, DL, Rašin, MR, Gunel, M, Davis, NR, Ercan-Sencicek, AG, Guez, DH, Spertus, JA, Leckman, JF, Dure IV, LS, Kurlan, R, Singer, HS, Gilbert, DL, Farhi, A, Louvi, A, Lifton, RP, Šestan, N & State, MW 2005, 'Medicine: Sequence variants in SLITRK1 are associated with Tourette's syndrome', Science, vol. 310, no. 5746, pp. 317-320. https://doi.org/10.1126/science.1116502
Abelson JF, Kwan KY, O'Roak B, Baek DY, Stillman AA, Morgan TM et al. Medicine: Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005 Oct 14;310(5746):317-320. https://doi.org/10.1126/science.1116502
Abelson, Jesse F. ; Kwan, Kenneth Y. ; O'Roak, Brian ; Baek, Danielle Y. ; Stillman, Althea A. ; Morgan, Thomas M. ; Mathews, Carol A. ; Pauls, David L. ; Rašin, Mladen Roko ; Gunel, Murat ; Davis, Nicole R. ; Ercan-Sencicek, A. Gulhan ; Guez, Danielle H. ; Spertus, John A. ; Leckman, James F. ; Dure IV, Leon S. ; Kurlan, Roger ; Singer, Harvey S. ; Gilbert, Donald L. ; Farhi, Anita ; Louvi, Angeliki ; Lifton, Richard P. ; Šestan, Nenad ; State, Matthew W. / Medicine : Sequence variants in SLITRK1 are associated with Tourette's syndrome. In: Science. 2005 ; Vol. 310, No. 5746. pp. 317-320.
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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.",
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AU - Farhi, Anita

AU - Louvi, Angeliki

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