Clinical trial NCT02628808: Susceptibility Genes in Autism Spectrum Disorders
Official title: Search of Susceptibility Genes in Autism Spectrum Disorders
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Autism Spectrum Disorders
Keywords: autism
asperger
Pervasive Developmental Disorder No Otherwise Specify
gene
polymorphism
mutation
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2015-12-11
Enrollment: 1616
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For all patients included in the study, .

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder
timeFrame: up to 12 months after completion of the inclusion and molecular explorations
Secondary outcomes:
measure: Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorders:
timeFrame: up to 12 months after completion of the inclusion and molecular explorations)
Other outcomes:
Locations:
city: Creteil
country: France
facility: Albert Chenevier Hospital
state: Ile De France
city: Paris
country: France
facility: Robert Debré Hospital
state: Ile De France
city: Bordeaux
country: France
facility: Centre de Ressources Autisme Aquitaine, CHU de Bordeaux
city: Grenoble
country: France
facility: CADIPA Centree hospitalier de Saint Egreve
city: Paris
country: France
facility: Cic Henri Mondor
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Marion Leboyer, M.D, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.