Search of Susceptibility Genes in Autism Spectrum Disorders
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Autism Spectrum Disorders
- Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- Enrollment
- 1616
- Locations
- 5
- Primary Endpoint
- Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
The main objective of the study is to define, for Autism Spectrum Disorder, the extent of genetic variation in synaptic pathways that may be targeted for therapeutic development. For this purpose the investigators will take advantage of large, well-characterized cohorts of patients with Autism Spectrum Disorder for genetic screenings. Targeted sequencing of selected synaptic genes, previously associated with Autism Spectrum Disorder, will be carried out in these cohorts with deep coverage of coding regions and a strong focus on previously untested regulatory regions. Genomic data from Copy Number Variant, whole genome sequencing and exome sequencing, available for some of these patients, will be integrated in the overall analysis. The investigators will strongly emphasize the establishment of comprehensive genotype/phenotype correlations and set up an induced Pluripotent Stem Cells collection from selected patients with synaptic mutations for functional and expression analysis.
Detailed Description
Specific aims are: Aim 1: To identify genetic variants in selected synaptic genes, by targeted sequencing with deep coverage of coding regions and a strong focus on previously untested regulatory regions in Autism Spectrum Disorder Aim 2: To define the range of clinical phenotypes caused by mutations in synaptic genes by establishing detailed genotype/phenotype correlations and analyzing segregation in families with multiple individuals affected by Autism Spectrum Disorder, Autism Spectrum Disorder traits or other neuropsychiatric disorders Aim 3: To generate a repository of induced Pluripotent Stem Cells from Autism Spectrum Disorder subjects with synaptic mutations for translational studies, including expression and functional assays. Aim 4: To identify the neuronal phenotypes caused by deleterious synaptic mutations for further translational studies
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis for Autism Spectrum Disorders or Autism using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria
Exclusion Criteria
- •Patients with profound intellectual disability or with a known medical cause of autism, such as neurocutaneous syndromes, Fragile X, metabolic disorders, extreme prematurity, congenital rubella and other prenatal or postnatal neurological infections or gross dysmorphology, will be excluded
Outcomes
Primary Outcomes
Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder
Time Frame: up to 12 months after completion of the inclusion and molecular explorations
Secondary Outcomes
- Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorders:(up to 12 months after completion of the inclusion and molecular explorations))