Sequence variants in SLITRK1 are associated with Tourette's syndrome

Science. 2005 Oct 14;310(5746):317-20. doi: 10.1126/science.1116502.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Adolescent
  • Animals
  • Attention Deficit Disorder with Hyperactivity / complications
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Brain / metabolism
  • Child
  • Child, Preschool
  • Chromosome Inversion
  • Chromosome Mapping
  • Chromosomes, Human, Pair 13*
  • DNA
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Sequence Analysis, DNA
  • Tourette Syndrome / complications
  • Tourette Syndrome / genetics*

Substances

  • 3' Untranslated Regions
  • Membrane Proteins
  • Nerve Tissue Proteins
  • SLITRK1 protein, human
  • DNA