Mutations Found in Nonsyndromic Mental Retardation

SYNGAP1 gene mutations occur in nonsyndromic mental retardation but not other mental disorders

WEDNESDAY, Feb. 4 (HealthDay News) -- Mutations in the SYNGAP1 gene, encoding a ras GTPase-activating protein, occur in patients with nonsyndromic mental retardation but not other conditions of mental retardation, according to research published in the Feb. 5 issue of the New England Journal of Medicine.

Fadi F. Hamdan, Ph.D., of the Centre Hospitalier Universitaire in Montreal, and colleagues evaluated the genetic abnormalities that appear in the SYNGAP1 gene, which has a role in development, synaptic plasticity and learning. The investigators sequenced the gene in 94 samples from patients with nonsyndromic mental retardation and compared these results to samples from 142 patients with autism spectrum disorder, 143 patients with schizophrenia and 190 control individuals.

Two patients with nonsyndromic mental retardation were identified as being heterozygous for nonsense mutations and one patient as heterozygous for a frame shift mutation in the SYNGAP1 gene. These were de novo mutations, as they were absent from DNA samples obtained from each patient's parents. All three of these patients had similar clinical profiles. Functional de novo mutations in the SYNGAP1 gene were not apparent in the control group, nor in patients with autism spectrum disorder or schizophrenia.

"The identification of genes associated with nonsyndromic mental retardation that encode proteins in well-characterized synaptic pathways offers the possibility of developing pharmacologic treatments to target associated complications, such as epilepsy, in addition to improving cognitive processes," the authors write.

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