title: De novo truncating mutation in Kinesin 17 associated with schizophrenia.
abstract: BACKGROUND
  Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. It is thought to be due to a complex interplay between polygenic and various environmental risk factors, although recent reports on genomic copy number variations suggest that a fraction of the cases could result from variably penetrant de novo variants. The gene encoding the synaptic motor protein kinesin 17 (KIF17) involved in glutamatergic synapse is a candidate gene for SCZ.
  
  
  METHODS
  As part of our Synapse to Disease project, we resequenced KIF17 in a cohort of individuals with sporadic SCZ (188 subjects). Additional populations included autism spectrum disorder (142 subjects), nonsyndromic mental retardation (95 subjects), and control subjects (568 subjects). Functional validation of the human mutation was done in developing zebrafish.
  
  
  RESULTS
  Here we report the identification of a de novo nonsense truncating mutation in one patient with SCZ, in kinesin 17, a synaptic motor protein. No de novo or truncating KIF17 mutations were found in the additional samples. We further validated the pathogenic nature of this mutation by knocking down its expression in zebrafish embryos, which resulted in a developmental defect.
  
  
  CONCLUSIONS
  Together our findings suggest that disruption of KIF17, although rare, could result in a schizophrenia phenotype and emphasize the possible involvement of rare de novo mutations in this disorder.
authors.affiliation: Department of Medicine, Center of Excellence in Neuromics of Université de Montréal, Centre Hospitalier de l'Université de Montreal Research Center, University of Montréal, Montreal, Quebec, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Tarabeux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Champagne
authors.forename: Edna
authors.initials: E
authors.lastname: Brustein
authors.forename: Fadi F
authors.initials: FF
authors.lastname: Hamdan
authors.forename: Julie
authors.initials: J
authors.lastname: Gauthier
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lapointe
authors.forename: Claudia
authors.initials: C
authors.lastname: Maios
authors.forename: Amélie
authors.initials: A
authors.lastname: Piton
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.forename: Edouard
authors.initials: E
authors.lastname: Henrion
authors.forename: Bruno
authors.initials: B
authors.lastname: Millet
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Delisi
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.forename: Ferid
authors.initials: F
authors.lastname: Fathalli
authors.forename: Eric
authors.initials: E
authors.lastname: Fombonne
authors.forename: Laurent
authors.initials: L
authors.lastname: Mottron
authors.forename: Nadine
authors.initials: N
authors.lastname: Forget-Dubois
authors.forename: Michel
authors.initials: M
authors.lastname: Boivin
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Lafrenière
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Krebs
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000328:Adult; D000818:Animals; D030801:Animals, Genetically Modified; D001321:Autistic Disorder / Q000235:genetics; D002461:Cell Line, Transformed; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D007814:Larva; D008297:Male; D009154:Mutation / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*; D014162:Transfection / Q000379:methods; D015027:Zebrafish
chemical_list: C485813:KIF17 protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D016547:Kinesins