Mutations in SYNGAP1 Cause Intellectual Disability, Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency

@article{Berryer2013MutationsIS,
  title={Mutations in SYNGAP1 Cause Intellectual Disability, Autism, and a Specific Form of Epilepsy by Inducing Haploinsufficiency},
  author={Martin H. Berryer and Fadi F. Hamdan and Laura Line Klitten and Rikke Steensbjerre M{\o}ller and Lionel Carmant and Jeremy A. Schwartzentruber and Lysanne Patry and Sylvia Dobrzeniecka and Daniel L. Rochefort and Mathilde Neugnot-Cerioli and Jean-Claude Lacaille and Zhiyv Niu and Christine M. Eng and Yaping Yang and Sylvain Palardy and C{\'e}line Belhumeur and Guy A. Rouleau and Niels Tommerup and Ladonna L Immken and Miriam H. Beauchamp and Gayle Simpson Patel and Jacek Majewski and Mark Andrew Tarnopolsky and Klaus Scheffzek and Helle Hjalgrim and Jacques L. Michaud and Graziella Di Cristo},
  journal={Human Mutation},
  year={2013},
  volume={34},
  url={https://api.semanticscholar.org/CorpusID:11397001}
}
This study confirms the involvement of SYNGAP1 in autism while providing novel insight into the epileptic manifestations associated with its disruption, and suggests that the de novo missense mutations, p.R579X, and possibly all the other truncating mutations in SYngAP1 result in a loss of its function.
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231 Citations

Identification of an individual with a SYNGAP1 pathogenic mutation in India

A case of a child of 2-year old with global developmental delay, microcephaly subtle dysmorphism, absence seizures, disrupted sleep, delay in learning a language, and eating problems is reported, the first SYNGAP1 heterozygous patient from Indian cohort.

Novel de novo heterozygous mutation on SYNGAP1 from the Indian population

The finding of a novel mutation in one of the genes, SYNGAP1 , implicated in ASD/ID is discussed and the current treatment prescribed to the patient and the progress of global developmental of the child is discussed.

De novo, heterozygous, loss‐of‐function mutations in SYNGAP1 cause a syndromic form of intellectual disability

Clinical features of the individuals reported here show significant overlap with those associated with 6p21.3 microdeletions, confirming that haploinsufficiency for SYNGAP1 is responsible for both disorders.

SYNGAP1 Mutation in Focal and Generalized Epilepsy: A Literature Overview and A Case Report with Special Aspects of the EEG

This case provides further support for efficacy of VPA in patients with SYNGAP1 mutation–related epilepsy and main clinical features of this 15-year-old nondysmorphic girl with intellectual disability are compatible with previous reports on patients withSYNG AP1 mutations.

Molecular and phenotypical findings of a novel de novo SYNGAP1 gene variant in an 11-year-old Iranian boy with intellectual disability.

The current study findings expand the existing knowledge of variants in SYNGAP1 that have been previously associated with nonsyndromic intellectual disability and autism, extending the spectrum of phenotypes associated with this gene.

Key roles of C2/GAP domains in SYNGAP1-related pathophysiology.

Novel Mutation of SYNGAP1 Associated with Autosomal Dominant Mental Retardation 5 in a Chinese Patient

A novel heterozygous variant in SYNGAP1 was discovered in a 4-year-old ethnic Chinese boy with ID and ASD but without seizures or malformation, and the c.509 + 1G > A mutation was present in a patient with MRD5.

Phenotype and genotype analyses of Chinese patients with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations

An investigation of SYNGAP1 mutations in a clinical cohort with ID and DD in Shandong, a northern province in China, to further explore the genotype and phenotype correlations and contributes to genetic counseling and therapeutic intervention for patients with MRD5.

Genetic and neurodevelopmental spectrum of SYNGAP1-associated intellectual disability and epilepsy

SYNGAP1 encephalopathy is characterised by early neurodevelopmental delay typically preceding the onset of a relatively recognisable epilepsy comprising generalised seizures (absences, myoclonic jerks) and frequent triggers.

De novo frameshift mutation in SYNGAP1 resulting in autosomal dominant mental retardation type 5 and autism spectrum disorder: a case report

W Whole-exome sequencing identified a de novo heterozygous frameshift mutation in the SYNGAP1 c.1230delC p.1230delC frameshift variant that has not been reported before, expanding clinicians' knowledge of the mutation spectrum and phenotypic variability linked to SYNGAP1, enhancing understanding of genotype-phenotype relationships in SYNGAP1-related conditions.
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31 References

De Novo SYNGAP1 Mutations in Nonsyndromic Intellectual Disability and Autism

A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA)

A patient with EMA and intellectual disability who carries a de novo balanced translocation is described, and the finding suggests that dysfunction of SYNGAP1 contributes to the development of generalized epilepsy, including EMA.

Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.

Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.

The results indicate that SYNGAP1 disruption is a cause of autosomal dominant nonsyndromic mental retardation.

Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population.

A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation

It is ascertained a carrier of a deletion encompassing SYNGAP1 among 300 patients with mental retardation studied by 1Mb array-comparative genomic hybridization (a-CGH).

Integrated analysis of clinical signs and literature data for the diagnosis and therapy of a previously undescribed 6p21.3 deletion syndrome

The present syndromic condition was not previously described and it can be regarded as a human model confirming the suggested biological properties of the genes included in the deletion interval, and modulation of the glutamate pathway as target of a therapeutic strategy for seizure control.

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This work identified and validated unique non-synonymous de novo mutations in nine genes and identified six likely to be pathogenic based on gene function, evolutionary conservation and mutation impact that could explain the majority of all mental retardation cases in the population.

Functional impact of global rare copy number variation in autism spectrum disorders

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