Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06260319 |
| Other study ID # |
C19-64 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2019 |
| Est. completion date |
January 1, 2024 |
Study information
| Verified date |
February 2024 |
| Source |
Institut National de la Santé Et de la Recherche Médicale, France |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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
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.
