Study of the Genetic Factors Involved in Autism and Related Disorders

Recruiting

• Conditions: Autism Spectrum Disorder
• Interventions: Genetic: DNA from subjects will be stored in the biobank of our study.

• Registration Number: NCT04727489
• 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.

Detailed Description

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 identify the neuronal phenotypes caused by deleterious synaptic mutations for further translational studies

Study Timeline

• Study First Submitted: 2021-01-20
• Study First Submitted QC: 2021-01-22
• Study First Posted: 2021-01-27
• Study Start: 2021-03-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-30
• Primary Completion: 2036-03
• Study Completion: 2036-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3800

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Relatives of probands with Autism Spectrum Disorder	DNA from subjects will be stored in the biobank of our study.	Relatives of probands with Autism Spectrum Disorder (N=1200 parents, N=600 siblings, N=300 other relatives) * Without Autism Spectrum Disorder diagnosis according to DSM-V, * With Autism Spectrum Disorder diagnosis according to DSM-V, and using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders
Autism Spectrum Disorder	DNA from subjects will be stored in the biobank of our study.	Probands with Autism Spectrum Disorder, (N=700), Diagnosis of ASD according to DSM-V criteria For all patients included in the study, core assessment carried out by either collaborating partners consists of diagnosis using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders. 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.
Control without Autism Spectrum Disorder	DNA from subjects will be stored in the biobank of our study.	Controls without Austim Spectrum Disorder, aged 6 to 40, N=2100 (300 adultes, 300 children) Healthy individuals with or without idiopathic surgical or urological conditions (e.g. orthopaedic conditions, hernia repairs, renal malformations, pre- or post-circumcision, phimosis, balanitis, scoliosis, congenital hip dislocation, adenoid or tonsil removal, dental procedures such as wisdom tooth extraction, cosmetic procedures such as removal of skin tags or cleft lip repairs, non-head injuries such as fractures, drainage of subungual or perichondrial haematomata).
Relatives of controls	DNA from subjects will be stored in the biobank of our study.	Relatives of controls without Autism Spectrum Disorder, N=400 first degree relatives

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	Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder

Secondary Outcome Measures

Name	Time	Method
Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorder	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 (6)

Albert Chenevier Hospital; 🇫🇷 Creteil, Ile De France, France

Centre de rehabilitation psychosociale, Hopital Saint Egreve; 🇫🇷 Grenoble, France

CRA, Hopital Charles Perrens, Bordeaux; 🇫🇷 Bordeaux, France

CIC, H. Mondor, Creteil; 🇫🇷 Créteil, France

CIC, CHU Bordeaux; 🇫🇷 Bordeaux, France

Robert Debré Hospital; 🇫🇷 Paris, Ile De France, France