title: 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.
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Abelson
authors.forename: Kenneth Y
authors.initials: KY
authors.lastname: Kwan
authors.forename: Brian J
authors.initials: BJ
authors.lastname: O'Roak
authors.forename: Danielle Y
authors.initials: DY
authors.lastname: Baek
authors.forename: Althea A
authors.initials: AA
authors.lastname: Stillman
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Morgan
authors.forename: Carol A
authors.initials: CA
authors.lastname: Mathews
authors.forename: David L
authors.initials: DL
authors.lastname: Pauls
authors.forename: Mladen-Roko
authors.initials: MR
authors.lastname: Rasin
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Davis
authors.forename: A Gulhan
authors.initials: AG
authors.lastname: Ercan-Sencicek
authors.forename: Danielle H
authors.initials: DH
authors.lastname: Guez
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.forename: James F
authors.initials: JF
authors.lastname: Leckman
authors.forename: Leon S
authors.initials: LS
authors.lastname: Dure
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlan
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Singer
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gilbert
authors.forename: Anita
authors.initials: A
authors.lastname: Farhi
authors.forename: Angeliki
authors.initials: A
authors.lastname: Louvi
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Nenad
authors.initials: N
authors.lastname: Sestan
authors.forename: Matthew W
authors.initials: MW
authors.lastname: State
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D004247:DNA; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D005879:Tourette Syndrome / Q000150:complications / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C505093:SLITRK1 protein, human; D004247:DNA