Study of the Genetic Factors Involved in Autism and Related Disorders (Gene&autism)

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.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Genetic: DNA from subjects will be stored in the biobank of our study.

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 Type: Observational
• Enrollment (Estimated): 3800

Contacts and Locations

• Study Contact: Name: Richard Delorme, M.D, Ph.D; Phone Number: +33662725334; Email: richard.delorme@aphp.fr
• Study Contact Backup: Name: Marion Leboyer, M.D, Ph.D; Phone Number: +33149813131; Email: marion.leboyer@inserm.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CIC, CHU Bordeaux
    • Contact: Michael Fayon, MD., PhD.; Phone Number: +33 (0)5 57 82 01 08; Email: michael.fayon@chu-bordeaux.fr
  • Bordeaux, France
    • Recruiting
    • CRA, Hopital Charles Perrens, Bordeaux
    • Contact: Mauel Bouvard, MD., PhD.; Phone Number: +33 (0)5 56 56 17 19; Email: bouvard.manuel@wanadoo.fr
  • Créteil, France
    • Not yet recruiting
    • CIC, H. Mondor, Creteil
    • Contact: Philippe Le Corvoisier, MD., PhD.; Phone Number: +33 (0)1 49 81 37 96; Email: philippe.lecorvoisier@inserm.fr
  • Grenoble
    • Grenoble, Grenoble, France
      • Not yet recruiting
      • Centre de rehabilitation psychosociale, Hopital Saint Egreve
      • Contact: Julien Dubreucq, MD.; Phone Number: +33 (0)4 76 56 44 40; Email: jdubreucq@ch-alpes-isere.fr
  • Île-de-France Region
    • Créteil, Île-de-France Region, France, 94000
      • Not yet recruiting
      • Albert Chenevier hospital
      • Contact: Marion Leboyer, MD., PhD.; Phone Number: +33 (0)1 49 81 32 90; Email: marion.leboyer@inserm.fr
    • Paris, Île-de-France Region, France, 75019
      • Not yet recruiting
      • Robert Debré Hospital
      • Contact: richard delorme, MD., PhD.; Phone Number: +33 (0)6 62 72 53 34; Email: richard.delorme@aphp.fr
      • Principal Investigator: richard Delorme, M.D,Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

For all patients included in the study

Description

Inclusion Criteria---------------------------------------------------------------------------------------------------

Probands with Autism Spectrum Disorder

• Meet the diagnostic criteria for ASD of the DSM-5 [American Psychiatric Association, 2013] based on a consensus between the clinical expertise of expert clinicians, the scores of the Autism Diagnostic Interview-Revised (ADI-R) (Rutter et al, 2003) and those of the Autism Diagnosis Observation Schedule (ADOS-2) (Lord et al, 2012)
• Be at least 24 months (no upper age limit)
• Somatic and Intellectual state compatible with a blood test
• Affiliation to the social insurance
• Signature of informed consent by the applicant or by holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Controls without ASD

• At least 24 months old
• Somatic and Intellectual state compatible with a blood test
• Affiliation to the social insurance
• Signature of informed consent by the subject or by holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Relatives of the probands with ASD or of controls without ASD

• At least 24 months old
• Somatic and Intellectual state compatible with a blood test
• Affiliation to the social insurance
• Signature of informed consent by the subject or by holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Exclusion Criteria --------------------------------------------------------------------------------------------------

Probands with Autism Spectrum Disorder

• Severe Intelectual Deficiency (IQ,35 or developmental age <18 months)

  ●. Personal psychiatric history (schizophrenia, bipolar disorder, substance use disorder (except tobacco), recurrent depression disorder, severe instable anxiety disorder)

• Personal neurologic history (epilepsy, or severe neurological disease)

Relatives of the probands with ASD, of the controls or the controls:

● Medical condition (psychiatric or somatic) not compatible with the inclusion

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Autism Spectrum Disorder; 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.	Genetic: DNA from subjects will be stored in the biobank of our study.; Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders.; Other Names: diagnostic test
Control without Autism Spectrum Disorder; 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).	Genetic: DNA from subjects will be stored in the biobank of our study.; Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders.; Other Names: diagnostic test
Relatives of probands with Autism Spectrum Disorder; 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	Genetic: DNA from subjects will be stored in the biobank of our study.; Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders.; Other Names: diagnostic test
Relatives of controls; Relatives of controls without Autism Spectrum Disorder, N=400 first degree relatives	Genetic: DNA from subjects will be stored in the biobank of our study.; Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders.; Other Names: diagnostic test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder	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

Outcome Measure	Measure Description	Time Frame
Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorder	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	up to 12 months after completion of the inclusion and molecular explorations

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Richard Delorme, M.D, Ph.D, Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

General Publications

• Delorme R, Ey E, Toro R, Leboyer M, Gillberg C, Bourgeron T. Progress toward treatments for synaptic defects in autism. Nat Med. 2013 Jun;19(6):685-94. doi: 10.1038/nm.3193. Epub 2013 Jun 6.

Helpful Links

• Description website of the sponsor

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Estimated): March 1, 2036
• Study Completion (Estimated): March 1, 2036

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: mutation; autism; polymorphism; gene; developmental Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Developmental Disabilities; Autistic Disorder
• Other Study ID Numbers: C16-89

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Study Protocol
2. Informed Consent Form

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No