Novel de novo SHANK3 mutation in autistic patients

Julie Gauthier, Dan Spiegelman, Amélie Piton, Ronald G. Lafreniére, Sandra Laurent, Judith St-Onge, Line Lapointe, Fadi F. Hamdan, Patrick Cossette, Laurent Mottron, Éric Fombonne, Ridha Joober, Claude Marineau, Pierre Drapeau, Guy A. Rouleau

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


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 mis-sense 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.

Original languageEnglish (US)
Pages (from-to)421-424
Number of pages4
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number3
StatePublished - Apr 5 2009
Externally publishedYes


  • Autism spectrum disorder
  • De novo
  • Pervasive developmental disorder
  • Splice site

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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