Contribution of New Generation Oxford Nanopore-type High-throughput Sequencing in the Diagnostic Strategy of Neurogenetic Diseases. (NEURONGS3)

Since 2012, NGS sequencing of long fragments or long reads has developed in various fields of research and today presents itself as a very promising alternative solution in the analysis of repeat amplifications. The Oxford Nanopore NGS automaton offers the prospect of bringing together 1st and 2nd line analyzes of all loci potentially indicated in neurogenetics at the same time. The project aims to compare the use of this new technology with methods currently used in reference laboratories.

The main objective is to evaluate the ability of next-generation high-throughput Oxford Nanopore-type sequencing (NEURONGS3) to diagnose 9 neurogenetic diseases compared to reference protocols via PCR (+/- Southern blot).

The secondary objective is to evaluate the repeatability of the NGS (intra-sample reproducibility) analysis in the diagnosis of 8 neurogenetic diseases.

Study Overview

• Status: Unknown
• Conditions: Neuro-Degenerative Disease
• Intervention / Treatment: Biological: Subject carrying an amplification of nucleotide repeats in one of the following 9 genes FMR1, DMPK, ZNF9, SCA2, JPH3, HD, FXN, C9ORF72, RFC1

Detailed Description

Since 2012, NGS sequencing of long fragments or long reads has developed in various fields of research and today presents itself as a very promising alternative solution in the analysis of repeat amplifications. The Oxford Nanopore NGS automaton offers the prospect of bringing together 1st and 2nd line analyzes of all loci potentially indicated in neurogenetics at the same time. The project aims to compare the use of this new technology with methods currently used in reference laboratories.

Multicenter cross-sectional early phase diagnostic study on already existing biological collections. Analyzes with the new technique (NGS) will be carried out blinded to the results obtained with the current reference algorithm based on the sequential performance of PCRs The main objective is to evaluate the ability of next-generation high-throughput Oxford Nanopore-type sequencing (NEURONGS3) to diagnose 9 neurogenetic diseases compared to reference protocols via PCR (+/- Southern blot).

The secondary objective is to evaluate the repeatability of the NGS (intra-sample reproducibility) analysis in the diagnosis of 8 neurogenetic diseases.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Cyril Goizet; Phone Number: 05 56 79 59 52; Email: cyril.goizet@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subject carrying an amplification of nucleotide repeats in one of the following 9 genes FMR1, DMPK, ZNF9, SCA2, JPH3, HD, FXN, C9ORF72, RFC1

Description

Inclusion Criteria:

• minors, adults and protected adults.
• Subject carrying an amplification of nucleotide repeats in one of the following 9 genes FMR1, DMPK, ZNF9, SCA2, JPH3, HD, FXN, C9ORF72, RFC1
• DNA available in sufficient quantity (5 to 10 µg)

Exclusion Criteria:

• DNA degraded or of medium size <30kb,
• Patient objection to research - This patient objection must be reached to the center's investigator within 1 maximum period of 1 month after sending the information note.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients tested positive by Next Generation Sequencing among all the patients tested positive by the current algorithm based on PCRs	For each of the 9 considered diseases, the proportion will be established as well as its 95% confidence interval.	through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the number of repetition amplifications found by the Next Generation Sequencing method and the number of repetition amplifications found by the PCR diagnosis method	For each of the 9 considered diseases, the number of repetition amplifications found by the Next Generation Sequencing method will be compared to the number of repetition amplifications found by the PCR diagnosis method using the Bland et Altman graphs. The average and standard deviation of the difference will be calculated.	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Cyril GOIZET, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2020
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: October 12, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): November 9, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurodegenerative Diseases
• Other Study ID Numbers: CHUBX 2019/51

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No