Decoding Developmental Disorders in Humams (devodecode)

Decoding Developmental Disorders in Humams, Devodecode

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

Study Overview

• Status: Completed
• Conditions: Genetic Diseases
• Intervention / Treatment: Genetic: Whole genome sequencing and Genome-Epigenome-Phenome Associations

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 720

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Institut Imagine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Pediatric and adult patients with hereditary diseases and related who have consented to the storage of their biological samples biological samples as part of the Institut Imagine's declared biological

Institut Imagine, selected on the basis of the following criteria :

- negative preliminary CGH or WES sequencing data

Description

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:

-

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary objectives	Establish a homogeneous cohort of patients with developmental developmental disorders to identify new genetic variants, and thus study the association between developmental pathologies and genetic variants.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
secondary objectives 1	Carry out WGS studies not only to refine exome 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	up to 2 years
secondary objectives 2	Develop precise preclinical models for functional studies of pathophysiological pathways.	up to 2 years

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Commissariat A L'energie Atomique; Imagine Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): January 1, 2024

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Estimated): February 15, 2024

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Developmental Disabilities; Genetic Diseases, Inborn
• Other Study ID Numbers: C19-64

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No