Functional Tests to Resolve Unsolved Rare Diseases. Rares.

NCT05696912 | Recruiting

• 1 other identifier: CHU BX 2021/40
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Variant of unknown significance; Functional genetics; Translational research; RNAseq; Gene expression regulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Pre-analysis process : Time of sample transport to the laboratory

  Inclusion visit

• Pre-analysis process : Quality of RNA extraction (RNA Integrity Number, RIN)

  Inclusion visit

• Praticability :Characteristics and number of CPU (Central Processing Unit)

  Inclusion visit

• Praticability : Training time of Biologists for interpretation

  Inclusion visit

• Global cost

  Inclusion visit

Study Arms (1)

Ex-vivo and In-vitro approach

OTHER

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

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

Interventions

Ex-vivo approach concerning 25 patients GENETIC

Ex-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis

Ex-vivo and In-vitro approach

In-vitro approach concerning 25 patients GENETIC

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

Ex-vivo and In-vitro approach

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Refusal to participate in research protocol.
• Patient under administrative supervision
• Pregnant or nursing women

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

Hopital Pellegrin

Bordeaux, 33000, France

RECRUITING

MeSH Terms

Conditions

Intellectual Disability; Rubinstein-Taybi Syndrome; Cystic Fibrosis; Heart Defects, Congenital; Periventricular Nodular Heterotopia; Pantothenate Kinase-Associated Neurodegeneration; Albinism

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Infant, Newborn, Diseases; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Malformations of Cortical Development, Group II; Malformations of Cortical Development; Nervous System Malformations; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Neuroaxonal Dystrophies; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Skin Diseases, Genetic; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Vincent MICHAUD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent MICHAUD

CONTACT

+335 57 82 01 93; vincent.michaud@chu-bordeaux.fr

Ndeye-Fatou NGOM

CONTACT

ndeye-fatou.ngom@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 7, 2022
• First Posted: January 25, 2023
• Study Start: January 30, 2023
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)