Functional Tests to Resolve Unsolved Rare Diseases. Rares. (RID)

University Hospital of Bordeaux

Status: Enrolling

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

Treatments: Genetic: In-vitro approach concerning 25 patients; Genetic: Ex-vivo approach concerning 25 patients

Study type: Interventional

Funder types: Other

Identifiers

NCT05696912

CHU BX 2021/40

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Ex-vivo and In-vitro approach

Other group

Description:

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 without specific samples needed for analysis in minigene or luciferase assay

Treatment:

Genetic: Ex-vivo approach concerning 25 patients

Genetic: In-vitro approach concerning 25 patients