Susceptibility Genes in Autism Spectrum Disorders

Search of Susceptibility Genes in Autism Spectrum Disorders

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorders

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 Type: Observational
• Enrollment (Actual): 1616

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Centre de Ressources Autisme Aquitaine, CHU de Bordeaux
  • Grenoble, France
    • CADIPA Centree hospitalier de Saint Egreve
  • Paris, France
    • Cic Henri Mondor
  • Île-de-France Region
    • Créteil, Île-de-France Region, France, 94000
      • Albert Chenevier hospital
    • Paris, Île-de-France Region, France, 75019
      • Robert Debré Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year 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:

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Autism Spectrum Disorder; 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.
controls; Age 2 to 65 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; Any familly members of included patient, aged of 2 or more. Exept persons with profound intellectual disability

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorders:	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: Marion Leboyer, 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.
• Latimier A, Kovarski K, Peyre H, Fernandez LG, Gras D, Leboyer M, Zalla T. Trustworthiness and Dominance Personality Traits' Judgments in Adults with Autism Spectrum Disorder. J Autism Dev Disord. 2019 Nov;49(11):4535-4546. doi: 10.1007/s10803-019-04163-1.
• Grea H, Scheid I, Gaman A, Rogemond V, Gillet S, Honnorat J, Bolognani F, Czech C, Bouquet C, Toledano E, Bouvard M, Delorme R, Groc L, Leboyer M. Clinical and autoimmune features of a patient with autism spectrum disorder seropositive for anti-NMDA-receptor autoantibody. Dialogues Clin Neurosci. 2017 Mar;19(1):65-70. doi: 10.31887/DCNS.2017.19.1/mleboyer.
• Amestoy A, Guillaud E, Bucchioni G, Zalla T, Umbricht D, Chatham C, Murtagh L, Houenou J, Delorme R, Moal ML, Leboyer M, Bouvard M, Cazalets JR. Visual attention and inhibitory control in children, teenagers and adults with autism without intellectual disability: results of oculomotor tasks from a 2-year longitudinal follow-up study (InFoR). Mol Autism. 2021 Nov 13;12(1):71. doi: 10.1186/s13229-021-00474-2.

Helpful Links

• website of the sponsor
• Site de transparence

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2009
• Primary Completion (Actual): December 3, 2021
• Study Completion (Actual): December 3, 2021

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: December 9, 2015
• First Posted (Estimated): December 11, 2015

Study Record Updates

• Last Update Posted (Estimated): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: mutation; autism; polymorphism; asperger; Pervasive Developmental Disorder No Otherwise Specify; gene
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: C07-33; 2008-A00019-46 (Registry Identifier: IDRCB)