NCT05696912

Functional Tests to Resolve Unsolved Rare Diseases. Rares.

Resolving Unsolved Rare Diseases : Functional Tests and New Diagnosis Strategy to Study Genetic Variants From High-throughput Sequencing (RID)

• Status: Unknown
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: University Hospital, Bordeaux · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Intellectual Disability
• Rubinstein-Taybi Syndrome
• Cystic Fibrosis
• Congenital Heart Defect
• Periventricular Nodular Heterotopia
• Neurodegeneration With Brain Iron Accumulation (NBIA)
• Albinism

Interventions

Type	Name	Description
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
GENETIC	In-vitro approach concerning 25 patients	In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay

Timeline

• Start date: 2023-01-30
• Primary completion: 2025-02-01
• Completion: 2025-02-01
• First posted: 2023-01-25
• Last updated: 2024-02-21

Locations

1 site across 1 country: France