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Previous Volume 360:599-605 February 5, 2009 Number 6 Next

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SUMMARY

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.

Source Information

From Centre Hospitalier Universitaire (CHU) Sainte-Justine Research Center (F.F.H., S.P., L.C., G.D., J.L.M.); Centre Hospitalier de l'Université de Montréal Research Center and the Department of Medicine (J.G., D.S., A.N., Y.Y., S.D., M.C., C.M., R.G.L., G.A.R.); Groupe de Recherche sur le Système Nerveux Central, Department of Pathology and Cell Biology (P.D.), the Department of Physiology (J.C.L.), and Centre de Recherche Fernand-Séguin, Hôpital Rivière-des-Prairies (E.P-L., L.M.) — all in the Centre of Excellence in Neuromics, Université de Montréal; the Department of Psychiatry, Montreal Children's Hospital (E.F.), and Douglas Mental Health University Institute (R.J.), McGill University — all in Montreal; the Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD (A.M.A., J.L.R.); the Center for Advanced Brain Imaging, Nathan S. Kline Institute, Orangeburg, NY (L.E.D.); and INSERM Unité 894, University Paris Descartes, and Sainte-Anne Hospital, Paris (M.-O.K., F.M.).

This article (10.1056/NEJMoa0805392) was updated on October 28, 2009, at NEJM.org.

Address reprint requests to Dr. Michaud at the Research Center, CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, QC H3T 1C5, Canada, or at jacques.michaud{at}recherche-ste-justine.qc.ca.

Full Text of this Article

This article has been cited by other articles:

• (2009). A New Genetics Pathway in Mental Retardation. JWatch Psychiatry 2009: 4-4 [Full Text]