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Genome Sequencing Strategies for Genetics Diagnosis of Patients With Intellectual Disability
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Summary
Introduction : Intellectual Disability (ID) is the most common cause of referral in the pediatric genetic centers and is characterized by an extreme genetic heterogeneity corresponding to a myriad of rare diseases that complicates the identification of ID's. Overall today in France, for non-syndromic ID affected patients, the Fra-X detection, the chromosomal microarray analysis and Gene Panel Strategy of 44 ID selected genes leads to a global diagnostic yield for 1/3 patients leaving 2/3 of patients still with no diagnosis. The advent, and burst, of Next Generation Sequencing (NGS) technologies has clearly revolutionized the approaches to diagnosis and research in the field of rare diseases at an international. That's why the main hypothesis of DEFIDIAG is that Whole Genome Sequencing (WGS) could allow to improve the diagnostic performance and cost-effectiveness for French patients with ID. Objective : The main objective of this study is to compare ther percentage of genetic causal diagnosis identified in ID patients by performing trio WGS analysis vs the use of the current French reference strategy (ACPA, X-Fra, DI 44). Methods and design : This is a prospective study. The investigators expect to include 1275 index case with his/her 2 biological unaffected parents.
Official title: Etude Pilote Des différentes stratégies de séquençage Haut débit du génome Pour le Diagnostic génétique Des Patients Atteints de déficience Intellectuelle
Key Details
Gender
All
Age Range
Any - Any
Study Type
INTERVENTIONAL
Enrollment
3825
Start Date
2020-03-13
Completion Date
2025-06-16
Last Updated
2026-06-23
Healthy Volunteers
Yes
Conditions
Interventions
Whole Genome Sequencing
The analysis will follow a consensus protocol that contains 3 obligatory steps: first of all, de novo variants (SNV, CNV and others SV) will be examined in the whole genome data set; then, a SNV/CNV/other SV analysis will be performed under a AR or X linked Mendelian mode hypothesis in the whole genomic regions of a OMIM extended list (that contains all genes already involved in human genetic diseases). Finally, analysis will focus on inherited pathogenic variants under an AD mode hypothesis (analysis of variations already reported as pathogenic in clinVar or HGMD pro; CNV or truncating variation in OMIM genes, etc). When these 3 steps analysis is completed then variants of interest identified at each step will be recorded until examination by a specific multidisciplinary meeting.
Locations (14)
CHU d'Angers
Angers, France
CHU Bordeaux
Bordeaux, France
Hospices Civil de Lyon
Bron, France
CHU Dijon
Dijon, France
CHU de Grenoble-Alpes
La Tronche, France
CHRU Lille
Lille, France
Assistance publique - Hôpitaux de Marseille
Marseille, France
CHU Montpellier
Montpellier, France
CHU Nantes
Nantes, France
Assistance publique - Hôpitaux de Paris - Groupe Hospitalier Pitié Salpétrière
Paris, France
Assistance publique - Hôpitaux de Paris - Hôpital Necker - Enfants malades
Paris, France
CHU Rennes
Rennes, France
CHU Rouen
Rouen, France
CHU Strasbourg
Strasbourg, France