Interest of High-throughput Sequencing of RNAs for the Diagnosis of Heterogeneous Genetic Diseases

NCT ID: NCT03971292

Last Updated: 2019-06-03

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 15 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-06-30
• Study Completion Date: 2022-07-31

Brief Summary

The advent of high throughput genomic DNA sequencing has led to major advances in the diagnosis of genetic diseases of heterogeneous origin. Thus, our hospital laboratory has developed in recent years several diagnostic tests based on the targeted sequencing of coding sequences of gene panels (from about twenty genes for DNA repair diseases to nearly five hundred genes for the intellectual disability). These targeted analyzes, carried out by capture, have thus solved 25 to 80% of the cases according to the indications, without allowing the diagnosis of the totality of the patients.

For these negative cases, the search for mutations in the coding sequences was then extended to Whole Exome Sequencing, thus providing several additional diagnoses.

Patients still remain without diagnosis after this exome study. These could be complex cases of genetic or even non-genetic origin, but also monogenic pathologies linked to mutations that are not identifiable by coding sequence analyzes, and especially affecting messenger RNAs.

Conditions

DNA Sequencing; Diagnosis of Genetic Diseases of Heterogeneous Origin

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Validation phase

The project will proceed in two phases: a validation test phase including 5 patients of known genotype and a prospective phase including 10 patients.

RNA sequencing

Intervention Type: GENETIC

Testing interest of messenger RNA sequencing for the etiological diagnosis of unresolved patients after sequencing coding regions.

Prospective phase

The project will proceed in two phases: a validation test phase including 5 patients of known genotype and a prospective phase including 10 patients.

RNA sequencing

Intervention Type: GENETIC

Testing interest of messenger RNA sequencing for the etiological diagnosis of unresolved patients after sequencing coding regions.

Interventions

RNA sequencing

Testing interest of messenger RNA sequencing for the etiological diagnosis of unresolved patients after sequencing coding regions.

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

• Patient minor or major
• Patient suffering from a pathology studied in the laboratory by high throughput sequencing: intellectual disability, myopathies, neurosensory disease (Bardet-Biedl syndrome, retinitis pigmentosa, ....), DNA repair diseases (Cockayne syndrome, ...)
• Sampling allowing the extraction of available RNA (or RNA available in the bank)
• Patient (or its legal representative) having already given their consent, on the one hand for carrying out genetic analyzes to determine the cause of their disease, and on the other hand for the conservation of part of their non used for further use in order to continue diagnostic investigations in the light of evolving knowledge and for research purposes.
• Patient (or its legal representative) agreeing to use data from his medical file and those associated with genetic diagnosis for research purposes
• Magnetic molecular diagnosis, after the usual investigations (high-throughput sequencing of a panel of genes on genomic DNA, sequencing of exome, or even genome.

◾ Refusal of the patient (or his / her legal representative) to participate in the study.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Les Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Countries

France

Facility Contacts

Nadège CALMELS

Role: primary

nadege.calmels@chru-strasbourg.fr

+33 33 69 55 07 77

Other Identifiers

7004

Identifier Type: -

Identifier Source: org_study_id