Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia
| Autor: | Ronald G. Lafrenière, Laurent Mottron, Mélanie Côté, Ousmane Diallo, Liliane Karemera, Edouard Henrion, Yan Yang, Sandra Laurent, Patrick Cossette, Marie-Odile Krebs, Anne Noreau, Claude Marineau, Judith L. Rapoport, Pierre Drapeau, Julien Tarabeux, Laurie Destroismaisons, Jolivet P, Eric Fombonne, Dan Spiegelman, Lynn E. DeLisi, Julie Gauthier, Amélie Piton, A Raymond, Duguay J, Lachapelle K, Kuku F, Ridha Joober, Lan Xiong, Guy A. Rouleau, Anjené M. Addington, Claudia Gaspar, Fadi F. Hamdan, Jean-Baptiste Rivière, Nathalie Champagne, Pascale Thibodeau |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Nerve Tissue Proteins Biology medicine.disease_cause Article MECP2 Cellular and Molecular Neuroscience Genes X-Linked Genetic variation medicine Humans Genetic Predisposition to Disease Child Monoamine Oxidase Molecular Biology Gene X chromosome Genetics Mutation Genetic Variation Sequence Analysis DNA medicine.disease Psychiatry and Mental health Monoamine neurotransmitter Child Development Disorders Pervasive Autism spectrum disorder Schizophrenia Synapses Female |
| Zdroj: | Molecular Psychiatry. 16:867-880 |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/mp.2010.54 |
| Popis: | 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 (n = 142; 122 males and 20 females) or SCZ (n = 143; 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). |
| Databáze: | OpenAIRE |
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