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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-A00019-46 | Registry Identifier | IDRCB |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| Measure | Description | 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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For all patients included in the study, .
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| Name | Affiliation | Role |
|---|---|---|
| Marion Leboyer, M.D, Ph.D | Institut National de la Santé Et de la Recherche Médicale, France | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre de Ressources Autisme Aquitaine, CHU de Bordeaux | Bordeaux | France | ||||
| CADIPA Centree hospitalier de Saint Egreve |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23744158 | Background | 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. | |
| 31123562 | Result | 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. |
| Label | URL |
|---|---|
| website of the sponsor | View source |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| D001321 | Autistic Disorder |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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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.
| Grenoble |
| France |
| Cic Henri Mondor | Paris | France |
| Albert Chenevier Hospital | Créteil | Île-de-France Region | 94000 | France |
| Robert Debré Hospital | Paris | Île-de-France Region | 75019 | France |
| 32929870 | 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. |
| 36495045 | 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. |
| 38012709 | 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. |
| 30814340 | 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. |
| 36464763 | 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. |
| 30006527 | 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. |
| 34774105 | 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. |
| 31418129 | Derived | 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. |
| 28566948 | 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. |
| Site de transparence | View source |
| This paper reports results | View source |