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COMPLETED
NCT04154891
NA

Genome Sequencing Strategies for Genetics Diagnosis of Patients With Intellectual Disability

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

View on ClinicalTrials.gov

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

Interventions

GENETIC

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