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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05696912
Other study ID # CHU BX 2021/40
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date January 30, 2023
Est. completion date February 2025

Study information

Verified date February 2024
Source University Hospital, Bordeaux
Contact Vincent MICHAUD
Phone +335 57 82 01 93
Email vincent.michaud@chu-bordeaux.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Rares diseases are a heterogeneous group of conditions which need important tools for diagnosis. The use of high-throughput sequencing is able to diagnose half of the patients. For the other part it is impossible to conclude due to the presence of variants of unknown significance (VOUS). Functional analysis are needed to bring strong argument to reclassify variants as pathogenic or benign. The main objective is to evaluate the diagnosis yield of this strategy.


Description:

The main objective is the improvement of the diagnosis of rare genetic diseases. The investigator lab is expert for diagnosis of some rare diseases such as neurodevelopmental disorder, albinism, cystic fibrosis and congenital heart defect. Actually with implementation of high-throughput sequencing for diagnosis, a high number of genetic variants are found and need to be interpretated. The ACMG classification is used to classify variants with argument of variant frequency, predicted effect on protein and in-silico prediction. Functional evidence is a strong argument to help classify VOUS. The investigators propose the use of RNA-Seq, minigene and luciferase assay for study of VOUS to bring argument to classify them as benign or pathogenic.


Recruitment information / eligibility

Status Recruiting
Enrollment 50
Est. completion date February 2025
Est. primary completion date February 2025
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria: - Minor and adult patient. - Registered for the social security system. - Informed consent signed by patient or parent of a minor patient. - Patient affected by one of the rare diseases studied (albinism, congenital heart defect, cystic fibrosis, neurodevelopmental disease) - Patient bearing variants of unknown significance (VOUS) Exclusion Criteria: - Refusal to participate in research protocol. - Patient under administrative supervision - Pregnant or nursing women

Study Design


Related Conditions & MeSH terms


Intervention

Genetic:
Ex-vivo approach concerning 25 patients
Ex-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis
In-vitro approach concerning 25 patients
In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay

Locations

Country Name City State
France Hopital Pellegrin Bordeaux

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of VOUS reclassified as pathogenic (class 5) or benign (class 1) It's the proportion of VOUS that could be definitively reclassified as pathogenic (class 5) or benign (class 1) according to the ACMG classification (Richards et al., 2015 and Appendix 1). Indeed currently only variants considered as pathogenic or probably pathogenic make it possible to confirm a diagnosis and to propose genetic offer genetic counseling to families and perform a prenatal diagnosis. This is an evaluation that will be carried out at the end of the analyses carried out Inclusion visit
Secondary Pre-analysis process : Time of sample transport to the laboratory Time of transport to the laboratory. To calculate this time, the time of collection and the time of receipt by the and the time of reception by the molecular genetics technician will be recorded Inclusion visit
Secondary Pre-analysis process : Quality of RNA extraction (RNA Integrity Number, RIN) RNA quality measurement by RIN (RNA integrity number): very good >7, good >/=5, poor <5. Only RNA with RIN >5 will be retained. Inclusion visit
Secondary Praticability :Characteristics and number of CPU (Central Processing Unit) Evaluation of bioinformatic ressources by measure of number of CPU needed and turnaround time for processing data Inclusion visit
Secondary Praticability : Training time of Biologists for interpretation Evaluation of training time needed to interpret the data Inclusion visit
Secondary Global cost Evaluation of cost of global analyse and each test Inclusion visit
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