Novel de novo SHANK3 mutation in autistic patients

Authors

  • Julie Gauthier,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Dan Spiegelman,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Amélie Piton,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Ronald G. Lafrenière,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Sandra Laurent,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Judith St-Onge,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Line Lapointe,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Fadi F. Hamdan,

    1. Division of Medical Genetics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada
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  • Patrick Cossette,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Laurent Mottron,

    1. Department of Psychiatry, Université de Montréal, Hôpital Rivière-des-Prairies, Montreal, Canada
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  • Éric Fombonne,

    1. Department of Psychiatry, McGill University and Montreal Children's Hospital, Montreal, QC, Canada
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  • Ridha Joober,

    1. Department of Psychiatry, McGill University and Douglas Hospital Research Centre, Montreal, QC, Canada
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  • Claude Marineau,

    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
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  • Pierre Drapeau,

    1. Department of Pathology and Cellular Biology, and Groupe de recherche sur le système nerveux central, Université de Montréal, Montreal, QC, Canada
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  • Guy A. Rouleau

    Corresponding author
    1. Centre of Excellence in Neuromics of Université de Montréal, CHUM Research Centre, Notre-Dame Hospital, Université de Montréal, Montreal, QC, Canada
    • Centre hospitalier de l'Université de Montréal, 2099, Alexandre De-Seve Street, Room Y-3633, Montreal, Quebec, Canada.
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  • Please cite this article as follows: Gauthier J, Spiegelman D, Piton A, Lafrenière RG, St-Onge J, Lapointe L, Hamdan FF, Cossette P, Mottron L, Fombonne É, Joober R, Marineau C, Drapeau P, Rouleau GA. 2009. Novel De Novo SHANK3 Mutation in Autistic Patients. Am J Med Genet Part B 150B:421–424.

Abstract

A number of studies have confirmed that genetic factors play an important role in autism spectrum disorder (ASD). More recently de novo mutations in the SHANK3 gene, a synaptic scaffolding protein, have been associated with the ASD phenotype. As part of our gene discovery strategy, we sequenced the SHANK3 gene in a cohort of 427 ASD subjects and 190 controls. Here, we report the identification of two putative causative mutations: one being a de novo deletion at an intronic donor splice site and one missense transmitted from an epileptic father. We were able to confirm the deleterious effect of the splice site deletion by RT-PCR using mRNA extracted from cultured lymphoblastoid cells. The missense mutation, a leucine to proline at amino acid position 68, is perfectly conserved across all species examined, and would be predicted to disrupt an alpha-helical domain. These results further support the role of SHANK3 gene disruption in the etiology of ASD. © 2008 Wiley-Liss, Inc.

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