Cited by 940Obsessive-Compulsive Spectrum DisordersGenetics and Neurodevelopmental DisordersGenomics and Rare Diseases

Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome

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. +16 more·2005·Science

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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Crossref · 10.1126/science.1116502

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  • Regional coexpression of miRNAs and their targets has been reported.

    “Regional coexpression of miRNAs and their targets has been reported.”

    From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Abelson et al. 2005

  • A mutation in the target site of miR-189 in the human SLITRK1 gene is associated with Tourette's syndrome.

    “For example, a mutation in the target site of miR-189 in the human SLITRK1 gene has been shown to be associated with Tourette's syndrome (Abelson et al. 2005)”

    From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Abelson et al. 2005

  • In our dataset, several genes carrying HHMCs and associated with basal ganglia functions stand out, like SLITRK1 and NOVA1.

    “in our dataset, several genes carrying HHMCs and associated with basal ganglia functions (critical for language and cognition) stand out, like SLITRK1114 and NOVA136,115–118 (Supplementary Information 4).”

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Authors
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, L. S., Kurlan, R., Singer, H. S., Gilbert, D. L., Farhi, A., Louvi, A., Lifton, R. P., Šestan, N., & State, M. W.
Affiliations
  • Yale University (US)
  • Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Harvard University (US)
  • University of Alabama at Birmingham (US)
  • University of Rochester Medicine (US)
  • Johns Hopkins University (US)
  • Cincinnati Children's Hospital Medical Center (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Abelson, Jesse F.
  • Kwan, Kenneth Y.
  • State, Matthew W.
Venue
Science
Published
2005-10-14
Volume
310
Issue
5746
Pages
317-320
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2114409847
Cited by
940
References
26
Citations by year
2026: 11 · 2025: 12 · 2024: 15 · 2023: 14 · 2022: 26 · 2021: 16 · 2020: 21 · 2019: 24 · 2018: 13 · 2017: 36 · 2016: 35 · 2015: 55 · 2014: 55 · 2013: 66 · 2012: 69
FWCI
90.63
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS054273, R01NS043520, R01 NS43520)
  • National Center for Research Resources (K23RR016118, K23 RR16118)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
Tourette syndrome, SLITRK1, genetic variants, frameshift mutation, microRNA binding sites, dendritic growth, neuronal development, candidate genes
MeSH terms
Adolescent, Animals, Attention Deficit Disorder with Hyperactivity, Brain, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 13, DNA, DNA Mutational Analysis, Female, Tourette Syndrome, Humans, Chromosome Inversion, Male, Membrane Proteins, Mutation, Nerve Tissue Proteins, Pedigree, Frameshift Mutation, In Situ Hybridization, Fluorescence, Sequence Analysis, DNA, 3' Untranslated Regions, Mice

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