Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.
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.
Hamdan
Fadi F
FF
Centre Hospitalier Universitaire Sainte-Justine Research Center, Centre of Excellence in Neuromics, Université de Montréal, QC, Canada.
Gauthier
Julie
J
Spiegelman
Dan
D
Noreau
Anne
A
Yang
Yan
Y
Pellerin
Stéphanie
S
Dobrzeniecka
Sylvia
S
Côté
Mélanie
M
Perreau-Linck
Elizabeth
E
Perreault-Linck
Elizabeth
E
Carmant
Lionel
L
D'Anjou
Guy
G
Fombonne
Eric
E
Addington
Anjene M
AM
Rapoport
Judith L
JL
Delisi
Lynn E
LE
Krebs
Marie-Odile
MO
Mouaffak
Faycal
F
Joober
Ridha
R
Mottron
Laurent
L
Drapeau
Pierre
P
Marineau
Claude
C
Lafrenière
Ronald G
RG
Lacaille
Jean Claude
JC
Rouleau
Guy A
GA
Michaud
Jacques L
JL
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
D018389:Codon, Nonsense; D020690:GTPase-Activating Proteins; C484739:SYNGAP1 protein, human; D020703:ras GTPase-Activating Proteins