Clinical trial NCT04727489: Study of the Genetic Factors Involved in Autism and Related Disorders
Official title: Study of the Genetic Factors Involved in Autism and Related Disorders
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Autism Spectrum Disorder
Keywords: autism
developmental Disorder
gene
polymorphism
mutation
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2021-01-27
Enrollment: 3800
Sex: ALL
Minimum age (years): 24
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.

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

Eligibility criteria: 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

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 Disorder
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: CIC, CHU Bordeaux
city: Bordeaux
country: France
facility: CRA, Hopital Charles Perrens, Bordeaux
city: Créteil
country: France
facility: CIC, H. Mondor, Creteil
city: Grenoble
country: France
facility: Centre de rehabilitation psychosociale, Hopital Saint Egreve
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Richard Delorme, 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.