Autism Spectrum Disorders
Conditions
Keywords
autism, asperger, Pervasive Developmental Disorder No Otherwise Specify, gene, polymorphism, mutation
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
Interventions
None listed
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Months to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORMarion Leboyer, M.D, Ph.D
Institut National de la Santé Et de la Recherche Médicale, France
Outcome results
None listed