Sequence variants in SLITRK1 are associated with Tourette's syndrome.
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.
Abelson
Jesse F
JF
Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Kwan
Kenneth Y
KY
O'Roak
Brian J
BJ
Baek
Danielle Y
DY
Stillman
Althea A
AA
Morgan
Thomas M
TM
Mathews
Carol A
CA
Pauls
David L
DL
Rasin
Mladen-Roko
MR
Gunel
Murat
M
Davis
Nicole R
NR
Ercan-Sencicek
A Gulhan
AG
Guez
Danielle H
DH
Spertus
John A
JA
Leckman
James F
JF
Dure
Leon S
LS
Kurlan
Roger
R
Singer
Harvey S
HS
Gilbert
Donald L
DL
Farhi
Anita
A
Louvi
Angeliki
A
Lifton
Richard P
RP
Sestan
Nenad
N
State
Matthew W
MW
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*
D020413:3' Untranslated Regions; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C505093:SLITRK1 protein, human; D004247:DNA