Susceptibility Genes in Autism Spectrum Disorders

Overview

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.

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

Conditions