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

• Conditions: DNA Sequencing; Diagnosis of Genetic Diseases of Heterogeneous Origin
• Interventions: Genetic: RNA sequencing

• Registration Number: NCT03971292
• Lead Sponsor: University Hospital, Strasbourg, France

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-05
• Study First Submitted: 2019-05-31
• Study First Submitted QC: 2019-05-31
• Last Update Submitted: 2019-05-31
• Study Start: 2019-06
• Study First Posted: 2019-06-03
• Last Update Posted: 2019-06-03
• Primary Completion: 2019-07
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Validation phase	RNA sequencing	The project will proceed in two phases: a validation test phase including 5 patients of known genotype and a prospective phase including 10 patients.
Prospective phase	RNA sequencing	The project will proceed in two phases: a validation test phase including 5 patients of known genotype and a prospective phase including 10 patients.

Primary Outcome Measures

Name	Time	Method
RNA sequencing	3 years	testing interest of messenger RNA sequencing for the etiological diagnosis of unresolved patients after sequencing of coding regions, and its integration into hospital routine in order to improve the diagnosis of heterogeneous genetic diseases.

Trial Locations

Locations (1)

Les Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France