Susceptibility Genes in Autism Spectrum Disorders
- Conditions
- Autism Spectrum Disorders
- Registration Number
- NCT02628808
- Lead Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1616
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder up to 12 months after completion of the inclusion and molecular explorations
- Secondary Outcome Measures
Name Time Method 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) The deleterious mutations that the investigators will identify in genes related to Autism Spectrum Disorders will help to have a comprehensive framework of biological pathways involved in Autism Spectrum Disorder
Trial Locations
- Locations (5)
Centre de Ressources Autisme Aquitaine, CHU de Bordeaux
🇫🇷Bordeaux, France
CADIPA Centree hospitalier de Saint Egreve
🇫🇷Grenoble, France
Cic Henri Mondor
🇫🇷Paris, France
Albert Chenevier Hospital
🇫🇷Creteil, Ile De France, France
Robert Debré Hospital
🇫🇷Paris, Ile De France, France