title: Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.
abstract: Although autosomal forms of nonsyndromic mental retardation account for the majority of cases of mental retardation, the genes that are involved remain largely unknown. We sequenced the autosomal gene SYNGAP1, which encodes a ras GTPase-activating protein that is critical for cognition and synapse function, in 94 patients with nonsyndromic mental retardation. We identified de novo truncating mutations (K138X, R579X, and L813RfsX22) in three of these patients. In contrast, we observed no de novo or truncating mutations in SYNGAP1 in samples from 142 subjects with autism spectrum disorders, 143 subjects with schizophrenia, and 190 control subjects. These results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation.
authors.affiliation: Centre Hospitalier Universitaire Sainte-Justine Research Center, Centre of Excellence in Neuromics, Université de Montréal, QC, Canada.
authors.forename: Fadi F
authors.initials: FF
authors.lastname: Hamdan
authors.forename: Julie
authors.initials: J
authors.lastname: Gauthier
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.forename: Anne
authors.initials: A
authors.lastname: Noreau
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pellerin
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dobrzeniecka
authors.forename: Mélanie
authors.initials: M
authors.lastname: Côté
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Perreau-Linck
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Perreault-Linck
authors.forename: Lionel
authors.initials: L
authors.lastname: Carmant
authors.forename: Guy
authors.initials: G
authors.lastname: D'Anjou
authors.forename: Eric
authors.initials: E
authors.lastname: Fombonne
authors.forename: Anjene 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: Faycal
authors.initials: F
authors.lastname: Mouaffak
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
authors.forename: Laurent
authors.initials: L
authors.lastname: Mottron
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
authors.forename: Claude
authors.initials: C
authors.lastname: Marineau
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Lafrenière
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Lacaille
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017422:Sequence Analysis, DNA; D020703:ras GTPase-Activating Proteins
chemical_list: D018389:Codon, Nonsense; D020690:GTPase-Activating Proteins; C484739:SYNGAP1 protein, human; D020703:ras GTPase-Activating Proteins