title: Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.
abstract: 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).
authors.affiliation: Department of Medicine, Centre of Excellence in Neuromics, CHUM Research Centre, University of Montreal, Montreal, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Piton
authors.forename: J
authors.initials: J
authors.lastname: Gauthier
authors.forename: F F
authors.initials: FF
authors.lastname: Hamdan
authors.forename: R G
authors.initials: RG
authors.lastname: Lafrenière
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Henrion
authors.forename: S
authors.initials: S
authors.lastname: Laurent
authors.forename: A
authors.initials: A
authors.lastname: Noreau
authors.forename: P
authors.initials: P
authors.lastname: Thibodeau
authors.forename: L
authors.initials: L
authors.lastname: Karemera
authors.forename: D
authors.initials: D
authors.lastname: Spiegelman
authors.forename: F
authors.initials: F
authors.lastname: Kuku
authors.forename: J
authors.initials: J
authors.lastname: Duguay
authors.forename: L
authors.initials: L
authors.lastname: Destroismaisons
authors.forename: P
authors.initials: P
authors.lastname: Jolivet
authors.forename: M
authors.initials: M
authors.lastname: Côté
authors.forename: K
authors.initials: K
authors.lastname: Lachapelle
authors.forename: O
authors.initials: O
authors.lastname: Diallo
authors.forename: A
authors.initials: A
authors.lastname: Raymond
authors.forename: C
authors.initials: C
authors.lastname: Marineau
authors.forename: N
authors.initials: N
authors.lastname: Champagne
authors.forename: L
authors.initials: L
authors.lastname: Xiong
authors.forename: C
authors.initials: C
authors.lastname: Gaspar
authors.forename: J-B
authors.initials: JB
authors.lastname: Rivière
authors.forename: J
authors.initials: J
authors.lastname: Tarabeux
authors.forename: P
authors.initials: P
authors.lastname: Cossette
authors.forename: M-O
authors.initials: MO
authors.lastname: Krebs
authors.forename: J L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: A
authors.initials: A
authors.lastname: Addington
authors.forename: L E
authors.initials: LE
authors.lastname: Delisi
authors.forename: L
authors.initials: L
authors.lastname: Mottron
authors.forename: R
authors.initials: R
authors.lastname: Joober
authors.forename: E
authors.initials: E
authors.lastname: Fombonne
authors.forename: P
authors.initials: P
authors.lastname: Drapeau
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D013569:Synapses / Q000235:genetics*
chemical_list: D009419:Nerve Tissue Proteins; D008995:Monoamine Oxidase