De novo truncating mutation in Kinesin 17 associated with schizophrenia.

Autor: Tarabeux J; 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., Champagne N, Brustein E, Hamdan FF, Gauthier J, Lapointe M, Maios C, Piton A, Spiegelman D, Henrion E, Millet B, Rapoport JL, Delisi LE, Joober R, Fathalli F, Fombonne E, Mottron L, Forget-Dubois N, Boivin M, Michaud JL, Lafrenière RG, Drapeau P, Krebs MO, Rouleau GA
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2010 Oct 01; Vol. 68 (7), pp. 649-56. Date of Electronic Publication: 2010 Jun 19.
DOI: 10.1016/j.biopsych.2010.04.018
Abstrakt: 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.
(Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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