Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia

A. Piton, J. Gauthier, F. F. Hamdan, R. G. Lafrenière, Y. Yang, E. Henrion, S. Laurent, A. Noreau, P. Thibodeau, L. Karemera, D. Spiegelman, F. Kuku, J. Duguay, L. Destroismaisons, P. Jolivet, M. Côté, K. Lachapelle, O. Diallo, A. Raymond, C. MarineauN. Champagne, L. Xiong, C. Gaspar, J. B. Rivière, J. Tarabeux, P. Cossette, M. O. Krebs, J. L. Rapoport, A. Addington, L. E. Delisi, L. Mottron, R. Joober, E. Fombonne, P. Drapeau, G. A. Rouleau

Research output: Contribution to journalArticlepeer-review

221 Scopus citations


Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n142; 122 males and 20 females) or SCZ (n143; 95 males and 48 females). We identified < 200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).

Original languageEnglish (US)
Pages (from-to)867-880
Number of pages14
JournalMolecular Psychiatry
Issue number8
StatePublished - Aug 2011
Externally publishedYes


  • X chromosome
  • autism spectrum disorder
  • rare variants
  • schizophrenia
  • synaptic genes

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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