Susceptibility Genes in Autism Spectrum Disorders

NCT02628808 | Completed DMC

• 2 other identifiers: C07-332008-A00019-46
• Study Type: observational
• Target: 1,616
• Locations: 1 country
• Sites: 5

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.

Conditions

Autism Spectrum Disorders

Keywords

autism; asperger; Pervasive Developmental Disorder No Otherwise Specify; gene; polymorphism; mutation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorders:

  up to 12 months after completion of the inclusion and molecular explorations)

Study Arms (3)

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

Eligibility Criteria

• Age: 18 Months - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

For all patients included in the study, .

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (5)

Centre de Ressources Autisme Aquitaine, CHU de Bordeaux

Bordeaux, France

Location

CADIPA Centree hospitalier de Saint Egreve

Grenoble, France

Location

Cic Henri Mondor

Paris, France

Location

Albert Chenevier Hospital

Créteil, Île-de-France Region, 94000, France

Location

Robert Debré Hospital

Paris, Île-de-France Region, 75019, France

Location

Related Publications (11)

• 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.

  PMID: 23744158 BACKGROUND

• Bennabi M, Tarantino N, Gaman A, Scheid I, Krishnamoorthy R, Debre P, Bouleau A, Caralp M, Gueguen S, Le-Moal ML, Bouvard M, Amestoy A, Delorme R, Leboyer M, Tamouza R, Vieillard V. Persistence of dysfunctional natural killer cells in adults with high-functioning autism spectrum disorders: stigma/consequence of unresolved early infectious events? Mol Autism. 2019 May 15;10:22. doi: 10.1186/s13229-019-0269-1. eCollection 2019.

  PMID: 31123562 RESULT

• Baltazar M, Geoffray MM, Chatham C, Bouvard M, Martinez Teruel A, Monnet D, Scheid I, Murzi E, Couffin-Cadiergues S, Umbricht D, Murtagh L, Delorme R, Ly Le-Moal M, Leboyer M, Amestoy A. "Reading the Mind in the Eyes" in Autistic Adults is Modulated by Valence and Difficulty: An InFoR Study. Autism Res. 2021 Feb;14(2):380-388. doi: 10.1002/aur.2390. Epub 2020 Sep 15.

  PMID: 32929870 RESULT

• Laidi C, Neu N, Watilliaux A, Martinez-Teruel A, Razafinimanana M, Boisgontier J, Hotier S, d'Albis MA, Delorme R, Amestoy A, Holiga S, Moal ML, Coupe P, Leboyer M, Houenou J, Rondi-Reig L, Paradis AL. Preserved navigation abilities and spatio-temporal memory in individuals with autism spectrum disorder. Autism Res. 2023 Feb;16(2):280-293. doi: 10.1002/aur.2865. Epub 2022 Dec 9.

  PMID: 36495045 RESULT

• Lefebvre A, Traut N, Pedoux A, Maruani A, Beggiato A, Elmaleh M, Germanaud D, Amestoy A, Ly-Le Moal M, Chatham C, Murtagh L, Bouvard M, Alisson M, Leboyer M, Bourgeron T, Toro R, Dumas G, Moreau C, Delorme R. Exploring the multidimensional nature of repetitive and restricted behaviors and interests (RRBI) in autism: neuroanatomical correlates and clinical implications. Mol Autism. 2023 Nov 27;14(1):45. doi: 10.1186/s13229-023-00576-z.

  PMID: 38012709 RESULT

• Holiga S, Hipp JF, Chatham CH, Garces P, Spooren W, D'Ardhuy XL, Bertolino A, Bouquet C, Buitelaar JK, Bours C, Rausch A, Oldehinkel M, Bouvard M, Amestoy A, Caralp M, Gueguen S, Ly-Le Moal M, Houenou J, Beckmann CF, Loth E, Murphy D, Charman T, Tillmann J, Laidi C, Delorme R, Beggiato A, Gaman A, Scheid I, Leboyer M, d'Albis MA, Sevigny J, Czech C, Bolognani F, Honey GD, Dukart J. Patients with autism spectrum disorders display reproducible functional connectivity alterations. Sci Transl Med. 2019 Feb 27;11(481):eaat9223. doi: 10.1126/scitranslmed.aat9223.

  PMID: 30814340 RESULT

• Lefebvre A, Tillmann J, Cliquet F, Amsellem F, Maruani A, Leblond C, Beggiato A, Germanaud D, Amestoy A, Ly-Le Moal M, Umbricht D, Chatham C, Murtagh L, Bouvard M, Leboyer M, Charman T, Bourgeron T, Delorme R, Dumas G; and the EU-AIMS LEAP group. Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways. Autism Res. 2023 Feb;16(2):364-378. doi: 10.1002/aur.2861. Epub 2022 Dec 4.

  PMID: 36464763 RESULT

• Safra L, Ioannou C, Amsellem F, Delorme R, Chevallier C. Distinct effects of social motivation on face evaluations in adolescents with and without autism. Sci Rep. 2018 Jul 13;8(1):10648. doi: 10.1038/s41598-018-28514-7.

  PMID: 30006527 RESULT

• 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.

  PMID: 34774105 RESULT

• 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.

  PMID: 31418129 DERIVED

• 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.

  PMID: 28566948 DERIVED

Related Links

• website of the sponsor
• Site de transparence
• This paper reports results

Biospecimen

Retention: SAMPLES WITH DNA

DNA from subjects will be stored in the biobank of our study. From some patients with deleterious mutations in synaptic genes, cells (PBMC, Keratinocytes ou Fibroblasts) will be sampled from derivation in Induced Pluripotent Stem Cells.

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Marion Leboyer, M.D, Ph.D

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: December 11, 2015
• Study Start: February 4, 2009
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: June 23, 2026

Record last verified: 2025-02

Locations

FR (5)