Official Title
Search of Susceptibility Genes in Autism Spectrum Disorders
Brief Title
Susceptibility Genes in Autism Spectrum Disorders
Protocol ID
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
Study Period
-
Enrollment Count
1,616 participants
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
Filters
Autism Spectrum Disorders
COMPLETED
CHILD
ADULT
OLDER_ADULT