title: De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia.
abstract: Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders.
authors.affiliation: Department of Medicine, Centre of Excellence in Neuromics of Université de Montréal, Centre Hospitalier de l'Université de Montréal Research Center, Université de Montréal, Montréal, QC H2L 2W5, Canada
authors.forename: Julie
authors.initials: J
authors.lastname: Gauthier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Champagne
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Lafrenière
authors.forename: Lan
authors.initials: L
authors.lastname: Xiong
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.forename: Edna
authors.initials: E
authors.lastname: Brustein
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lapointe
authors.forename: Huashan
authors.initials: H
authors.lastname: Peng
authors.forename: Mélanie
authors.initials: M
authors.lastname: Côté
authors.forename: Anne
authors.initials: A
authors.lastname: Noreau
authors.forename: Fadi F
authors.initials: FF
authors.lastname: Hamdan
authors.forename: Anjené M
authors.initials: AM
authors.lastname: Addington
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Delisi
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Krebs
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.forename: Ferid
authors.initials: F
authors.lastname: Fathalli
authors.forename: Fayçal
authors.initials: F
authors.lastname: Mouaffak
authors.forename: Ali P
authors.initials: AP
authors.lastname: Haghighi
authors.forename: Christian
authors.initials: C
authors.lastname: Néri
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dubé
authors.forename: Mark E
authors.initials: ME
authors.lastname: Samuels
authors.forename: Claude
authors.initials: C
authors.lastname: Marineau
authors.forename: Eric A
authors.initials: EA
authors.lastname: Stone
authors.forename: Philip
authors.initials: P
authors.lastname: Awadalla
authors.forename: Philip A
authors.initials: PA
authors.lastname: Barker
authors.forename: Salvatore
authors.initials: S
authors.lastname: Carbonetto
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology*; D010375:Pedigree; D051381:Rats; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015027:Zebrafish
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human; C033652:postsynaptic density proteins
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