Decoding Developmental Disorders in Humams

NCT ID: NCT06260319

Last Updated: 2024-02-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

720 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-01

Study Completion Date

2024-01-01

Brief Summary

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The DEVO-DECODE project aims to align our currently limited knowledge currently limited knowledge of the genetic architecture of developmental with our more advanced knowledge of their "phenome".

To this end, we aim to establish a homogeneous cohort of patients with with developmental disorders to identify new genetic variants genetic variants, and thus study the association between developmental and genetic variants. Secondary objectives are:2

* Carry out WGS studies not only to refine exosomal sequencing data exome sequencing data, but above all to identify and validate non-coding non-coding DNA alterations, in both transcribed and non-transcribed transcribed or non-transcribed genomic domains
* Develop precise preclinical models for functional studies of pathophysiological pathways

Detailed Description

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Developmental disorders, which encompass congenital anomalies and intellectual disabilities - including autism spectrum disorders - constitute a vast group of pathologies, caused by a complex set of genetic and environmental factors. They can affect several organs or tissues, such as brain abnormalities, head and neck malformations, heart defects, skeletal disorders and ophthalmological or hearing pathologies. They occur in around 2-3% of live births - affecting around 150,000 newborns every year in Europe (1). These pathologies are associated with high morbidity and mortality rates. They were responsible for 632,000 deaths worldwide in 2013 (2), representing a major social, economic and health problem.

Together, these diseases represent a considerable challenge in terms of medical care and genetic counseling, underlining the major deficits in fundamental and clinical knowledge to date.

At the Hôpital Necker-Enfants malades and the Institut des Maladies Génétiques Imagine, between 20,000 and 25,000 patients suffering from a wide range of developmental disorders are treated every year. Multidisciplinary consultations, together with state-of-the-art genomic investigations such as comparative genome hybridization (CGH) and whole exome sequencing (WES), provide the research and clinical teams involved with in-depth knowledge of the natural history of these diseases and the phenotypes of affected patients, as well as a better understanding of their genetic basis. Despite this, the rate of unknown diagnoses is very high (over 65-70% of cases remain without a distinct pathophysiological label), due to both the heterogeneity of these diseases and the complexity of their genetic architecture, probably involving non-coding DNA in many cases. Studying this non-coding DNA therefore requires technologies such as whole genome sequencing (WGS).

The main aim of the DEVO-DECODE project is to align our currently limited knowledge of the genetic architecture of developmental disorders with our more advanced knowledge of their "phenome". To meet this challenge,we propose to draw on the expertise and resources available within the research and clinical teams at Institut Imagine and Hôpital Necker, in order to:

1. create well-characterized, homogeneous cohorts.
2. systematize the collection of samples from patient care for biobanking and other studies.
3. carry out WGS studies not only to refine exome sequencing data, but above all to identify and validate non-coding DNA alterations, in both transcribed and non-transcribed genomic domains.
4. develop precise preclinical models for functional studies of candidate pathophysiological pathways.

Conditions

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Genetic Diseases

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

RETROSPECTIVE

Interventions

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Whole genome sequencing and Genome-Epigenome-Phenome Associations

* Whole genome sequencing (WGS) and bioinformatics analysis
* Functional validation
* Genome-Epigenome-Phenome Associations

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* Pediatric and adult patients with hereditary diseases and relatives who have consented to the storage of their biological samples in the Institut Imagine's declared biological collections.
* Pediatric and adult patients with hereditary diseases and relatives who have been informed of the research project and who have not objected to the re-use of their data and biological samples samples

Exclusion Criteria

\-
Minimum Eligible Age

1 Year

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Imagine Institute

OTHER

Sponsor Role collaborator

Commissariat A L'energie Atomique

OTHER_GOV

Sponsor Role collaborator

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

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Institut Imagine

Paris, , France

Site Status

Countries

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France

Other Identifiers

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C19-64

Identifier Type: -

Identifier Source: org_study_id

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