Diagnostic Research in Patients With Rare Diseases -Solving the Unsolved Rare Diseases (AnDDI-Solve-RD)

Most diagnostically unsolved rare disease have a genetic cause. These causes have not been found applying the current methodologies due to technical limitations (e.g. repeat expansions, changes in non-coding (intronic) regions) or, although methodically recorded, their pathophysiological significance but not classified as clinically relevant. A re- and meta-analysis of existing data sets with new algorithms and statistical models as well as the complementation with other omics technologies followed by functional follow-up studies in appropriate disease models (e.g. patient cell lines) allows to elucidate additional causes of diseases and improve the diagnosis of hereditary diseases. In addition to the direct examination of persons affected, the analysis of healthy family members, for example of parents, plays an important role in a so-called trio analysis, especially in the efficient filtering of the extensive data sets for newly created changes, so-called de novo- Variants (new mutations). In the context of the outlined analyzes, new disease genes can be found and validated. The gain of scientific knowledge due to a better understanding of basic cell biological mechanisms can contribute to the development of targeted therapeutic approaches.

In this context, the Solve-RD project has been built and financed by the European Union with the ambitions to solve large numbers of rare disease, for which a molecular cause is not known yet by sophisticated combined omics approaches, and to improve diagnostics of rare disease patients. Solve-RD fully integrates with the newly formed European Reference Networks (ERNs) for rare diseases, and in particular the ERN-RND, -EURO-NMD, -ITHACA, and -GENTURIS. The AnDDI-Rares network is fully affiliated to the ERN ITHACA network and will actively contribute to the project, by the ambition of sharing knowledge about genes, genomic variants and phenotypes.

The project will first reanalyse 18.000 negative exomes from the different ERNs performed in a diagnostic or research context (collection of biomaterial, clinical/phenotypic data plus next-generation sequencing has already been performed, and the patient/family has agreed previously in writing that their sample could be used for research related to their disease, with no study related presence required. The project will also propose new multi-omics analyses with new samples needed in 500 patients and their parents in total, justifying the AnDDI-Solve-RD project.

Study Overview

• Status: Recruiting
• Conditions: Rare Diseases
• Intervention / Treatment: Biological: Biological samples; Genetic: Genetic test

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Laurence OLIVIER-FAIVRE; Phone Number: +33 03.80.29.53.13; Email: laurence.faivre@chu-dijon.fr

Study Locations

• France
  • Dijon, France, 21079
    • Recruiting
    • CHU de Dijon
    • Contact: Laurence OLIVIER-FAIVRE; Phone Number: 03.80.29.53.13; Email: laurence.faivre@chu-dijon.fr
    • Contact: laurence OLIVIER-FAIVRE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with rare diseases

Description

Inclusion Criteria:

• Persons or legal guardian who have given their written informed consent
• Unclear molecular cause of the disease corresponding to the list of diseases selected by the Solve-RD data interpretation force (principal investigator part of the team)
• Suspected genetic cause of the disease with negative exome reanalysis
• Healthy parents available for trio analysis

Exclusion Criteria:

• Person not affiliated to a national health insurance scheme

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
index cases and their parents	Biological: Biological samples; blood samples, urine samples, tissue samples; Genetic: Genetic test; anamnesis and NGS sequencing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular genetic	Verification of the genetic causes of unclear genetic diseases	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of diagnoses	Improve number of diagnoses of unclear syndromes	Day 1
Characterization of gene defects	Further characterization of the identified gene defects	Day 1
Number of patients receiving appropriate therapy after successful diagnosis		Day 1

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2019
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 18, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Rare Diseases
• Other Study ID Numbers: OLIVIER-FAIVRE H2020 2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No