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 Farhi; Angeliki Louvi; Richard P. Lifton; Nenad Šestan; Matthew W. State

doi:10.1126/science.1116502

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 language	English (US)
Pages (from-to)	317-320
Number of pages	4
Journal	Science
Volume	310
Issue number	5746
DOIs	https://doi.org/10.1126/science.1116502
State	Published - Oct 14 2005
Externally published	Yes

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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

Abelson, JF, Kwan, KY, O'Roak, BJ, 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

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title = "Medicine: Sequence variants in SLITRK1 are associated with Tourette's syndrome",

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.",

author = "Abelson, {Jesse F.} and Kwan, {Kenneth Y.} and O'Roak, {Brian J.} and Baek, {Danielle Y.} and Stillman, {Althea A.} and Morgan, {Thomas M.} and Mathews, {Carol A.} and Pauls, {David L.} and Ra{\v s}in, {Mladen Roko} and Murat Gunel and Davis, {Nicole R.} and Ercan-Sencicek, {A. Gulhan} and Guez, {Danielle H.} and Spertus, {John A.} and Leckman, {James F.} and {Dure IV}, {Leon S.} and Roger Kurlan and Singer, {Harvey S.} and Gilbert, {Donald L.} and Anita Farhi and Angeliki Louvi and Lifton, {Richard P.} and Nenad {\v S}estan and State, {Matthew W.}",

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T2 - Sequence variants in SLITRK1 are associated with Tourette's syndrome

AU - Abelson, Jesse F.

AU - Kwan, Kenneth Y.

AU - O'Roak, Brian J.

AU - Baek, Danielle Y.

AU - Stillman, Althea A.

AU - Morgan, Thomas M.

AU - Mathews, Carol A.

AU - Pauls, David L.

AU - Rašin, Mladen Roko

AU - Gunel, Murat

AU - Davis, Nicole R.

AU - Ercan-Sencicek, A. Gulhan

AU - Guez, Danielle H.

AU - Spertus, John A.

AU - Leckman, James F.

AU - Dure IV, Leon S.

AU - Kurlan, Roger

AU - Singer, Harvey S.

AU - Gilbert, Donald L.

AU - Farhi, Anita

AU - Louvi, Angeliki

AU - Lifton, Richard P.

AU - Šestan, Nenad

AU - State, Matthew W.

PY - 2005/10/14

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N2 - 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.

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

Abstract

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