@article{92e1b090f22842fdae89aee419cfbe7e,
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.",
keywords = "De novo, KIF17, NMDA, kinesin, schizophrenia, synapse",
author = "Julien Tarabeux and Nathalie Champagne and Edna Brustein and Hamdan, {Fadi F.} and Julie Gauthier and Mathieu Lapointe and Claudia Maios and Amlie Piton and Dan Spiegelman and {\'E}douard Henrion and Bruno Millet and Rapoport, {Judith L.} and Delisi, {Lynn E.} and Ridha Joober and Ferid Fathalli and {\'E}ric Fombonne and Laurent Mottron and Nadine Forget-Dubois and Michel Boivin and Michaud, {Jacques L.} and Lafrenire, {Ronald G.} and Pierre Drapeau and Krebs, {Marie Odile} and Rouleau, {Guy A.}",
note = "Funding Information: This work was supported by Genome Canada and G{\'e}nome Qu{\'e}bec and received cofunding from Universit{\'e} de Montr{\'e}al for the Synapse to Disease project, as well as funding from the Canadian Foundation for Innovation. JT receives a scholarship from the Universit{\'e} Paris Descartes (joint program Universit{\'e} Paris Descartes—Universit{\'e} de Montr{\'e}al). GAR holds the Canada Research Chair in Genetics of the Nervous System; PD holds the Canada Research Chair in Neuroscience. JLM is a recipient of the Clinical Investigator Award of Canadian Institutes of Health Research. The Synapse to Disease team is composed of the following additional members: Isabelle Bachand, Marjolaine Chicoine, M{\'e}lanie C{\^o}t{\'e}, Kathleen Daignault, Anne Desjarlais, Ousmane Diallo, Sylvia Dobrzeniecka, Joannie Duguay, Marina Drits, Philippe Jolivet, Liliane Karamera, Fr{\'e}d{\'e}ric Kuku, Karine Lachapelle, Guy Lalibert{\'e}, Sandra Laurent, Annie Levert, Meijiang Liao, Claude Marineau, Carlos Marino, Anne Noreau, Huashan Peng, Annie Raymond, Annie Reynolds, Daniel Rochefort, Judith St-Onge, Pascale Thibodeau, Kazuya Tsurudome, Yan Yang, Sophie Leroy, Katia Ossian, M{\'e}lanie Chayet, and F. Mouaffak. ",
year = "2010",
month = oct,
day = "1",
doi = "10.1016/j.biopsych.2010.04.018",
language = "English (US)",
volume = "68",
pages = "649--656",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "7",
}