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Research Article Summaries

Below, we've summarized several research articles that include information about SYNGAP1. We hope you find this information helpful! As we learn more from children who have these gene changes, we expect this list of resources and information to grow.


The SYNGAP1 gene is responsible for regulating a major signaling protein for receptors in the brain. In their recent study, Jeyabalan and Clement used mouse models to study brain development and function in relation to SYNGAP1 mutations. They found that mutations of the SYNGAP1 gene can lead to less SYNGAP1 protein production.  Protein depletion by 50% or more is enough to cause abnormal brain development and function, which can in turn lead to developmental delays and intellectual disabilities. Researchers still have more questions to answer about other proteins that may be affected by the SYNGAP1 mutation. Studies such as this can lead to development of therapeutic interventions during critical developmental stages of life. 

  • Parker et al., 2015 – De novo, heterozygous, loss-of-function mutations in SYNGAP1cause a syndromic form of intellectual disability

    A previous study done by Hamdan et al. (2009) identified three de novoSYNGAP1 mutations, linking them to intellectual disability (ID) and describing them as nonsyndromic, or unrelated to any specific syndrome or condition. Through exome sequencing of ten affected individuals and their parents, the more recent study done by Parker et al. was able to identify 8 SYNGAP1 mutations and 1 SYNGAP1 deletion in individuals with undiagnosed developmental disorders. Ranging from age 3 to age 14, the affected individuals all exhibited a range of developmental delays and distinct facial features. A majority of the affected individuals exhibited behavior problems, such as aggression and excitability, and seven of the ten individuals were also reported as having seizures. While the features exhibited in the individuals with a SYNGAP1 mutation or deletion varied, Parker et al. suggest that the clinical features seen in affected individuals (see table below) are consistent enough to point to the potential diagnosis of a syndrome caused by SYNGAP1 mutations.  However, more clinical research with a larger group of SYNGAP1 patients will be needed to determine the degree to which this genetic change affects medical, behavioral, and developmental aspects of the individual. 

  • O’Roak et al., 2014Recurrent de novo mutations implicate novel genes underlying simplex autism risk

    Researchers resequenced 64 risk genes in nearly 6,000 individuals from families that have one child affected with Autism Spectrum Disorder (ASD). Those affected were compared to their unaffected siblings. Individuals that had previous whole exome sequencing were included, as well as those without previous sequencing performed. Candidate genes to resequence were selected based on previously published reports and the researcher’s own unpublished data. Researchers were able to identify new – orde novo­- mutations in nine genes linked to autism risk, one of which is SYNGAP1. De novo mutations of SYNGAP1 have been observed in patients with intellectual disability (ID), who may or may not have symptoms of ASD or experience seizures, and in patients with epileptic disorders of the brain, with or without autism. Affected individuals who were found to have a mutation of SYNGAP1 exhibited a lower intelligence quotient (IQ) and an increased likelihood of seizures. 

    The goal of this research is to expand our understanding of the biology of these conditions as well as help move towards more precise treatment for patients. This is another example of how Simons VIP Connect helps aid in obtaining this knowledge. DNA samples for this study were obtained from the Rutgers University Cell and DNA Repository that Simons VIP participants provide samples to voluntarily. Simons VIP Connect is grateful for the families that participate in the project, this work could not be completed without you. 

  • Dyment et al., 2014 - Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: A retrospective study
    FORGE (Finding Of Rare disease GEnes) and Care4Rare from Canada conducted a study that examined rare forms of epilepsy with a panel of genes associated with epilepsy disorders.  Of the nine families who participated, eight were found to have different genetic mutations associated with epilepsy.  In one person, a deletion in the SYNGAP1 gene was found. This person had intellectual disability, coordination issues, and absence and atonic epilepsy.

  • Purcell et al., 2014 - A polygenic burden of rare disruptive mutations in schizophrenia
    This study screened over 5,000 individuals from a population in Sweden for about 2,500 genes that are candidates for autism and intellectual disability. One patient diagnosed with autism was found to have a mutation in SYNGAP1 that was not present in either parent (de novo).

  • Yang et al. 2013 - Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders
    In this study, whole exome sequencing was used to search for genetic causes to unexplained developmental delay, intellectual disability, and neurological differences in 250 children. One child had a mutation in the SYNGAP1 gene that is believed to be the cause of his intellectual disability.

  • Berryer et al., 2013 - Mutations in SYNGAP1 cause intellectual disability, autism and a specific form of epilepsy by inducing haploinsufficiency
    In this paper, we learn that SYNGAP1 plays an important role in a person’s learning and memory and may have implications in children with intellectual disabilities and/or autism. The majority of this article focuses on understanding how each mutation affects the gene’s ability to function, however, the behavioral, physical, and intellectual characteristics of these individuals are described in detail in the supplementary materials.

    Five individuals with damaging variations (mutations) in the SYNGAP1 gene are described in this paper. Of the participants involved in this study, all five had some degree of intellectual disability, ranging from mild to moderate/severe. One individual (who was three at the time of evaluation) had no speech. Two others had some degree of speech/language delay. Four of the participants had an MRI, and all were normal. Three of the five reported some type of “abnormal” behavior, which included sleep difficulty, behavior issues, and/or psychological concerns.

  • deLigt et al., 2012 - Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability
    In this study, 100 patients with severe intellectual disability (and their unaffected parents) underwent exome sequencing to attempt to identify a genetic cause for their diagnosis. Further analysis was performed for five genes that have been associated with intellectual disability (DYNC1H1, GATAD2B, ASH11, KIFSC and CTNNB1) in 765 additional patients with intellectual disability. One individual described in this study had moderate to severe ID, epilepsy, speech delay/absent speech, subtle differences in facial features, and sleep disturbances.

  • Rauch et al., 2012 - Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study
    The SYNGAP1 gene plays an important role in the brain’s development. Changes in this gene have been previously linked to intellectual disability, and this study confirms that finding. The researchers suggest that changes in the SYNGAP1 gene may be found in as many as 2% of children with non-specific intellectual disability. Changes in this gene are not often inherited.

  • Xu et al., 2012 - De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia
    The goal of this article was to find evidence of new genetic changes that may be related to brain function and schizophrenia. Families from both South African descent and European descent were included in the study. One person, who had been diagnosed with schizophrenia, was found to have a genetic change in SYNGAP1.

  • Vissers et al., 2010 - A de novo paradigm for mental retardation (please note: "mental retardation" is out-of-date terminology; we now use the term "intellectual disability")
    SYNGAP1 gene mutations are associated with intellectual disability (ID).  This report describes a how a SYNGAP1 mutation was identified in a patient through whole exome sequencing. This finding was not observed in either parent (this is called “de novo”) and is likely causative of the patient’s intellectual disability.

You can also visit SFARI's website to see information for researchers about this gene. SFARIgene: SYNGAP1

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