Validation of a Clinical Algorithm for the Diagnosis of Recessive Ataxias

NCT04099914 | Completed

• 1 other identifier: RECHMPL18_0431
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The field of clinical diagnosis of recessive cerebellar ataxias (ARCA) is particularly complex and Next Generation Sequencing (NGS) techniques have revolutionized this neuro-genetic field. The current challenge is to optimize the analysis of genetic data generated by NGS because: the processing of data remains very laborious; diagnostic yeld less than 50%; the interpretation of the variants sometimes very difficult. For this purpose of optimization, the team of the University Hospital of Strasbourg has developed a computer algorithm based on 124 clinical and para-clinical parameters (derived from the data of the literature), useful to guide the genes to be targeted in priority by genetic analysis, in the context of a suspicion of ARCA (\> 60 known genes); this algorithm was validated retrospectively in 834 patients with genetically confirmed ARCA (92% Sense, 95% Spec). However, these 834 patients are often the same as those described in the literature and used for the elaboration of the algorithm. This introduces a bias in the initial evaluation of the algorithm, which therefore requires validation in clinical practice, from a cohort of patients referred for suspected ARCA (with or without a found genetic mutation). At the same time, Montpellier's genetics laboratory has developed a bioinformatic method for the search for copy number variations (CNV) that can be applied in a targeted manner to the genes predicted by the algorithm. The principal aim of this study is the validation of a semi-automated clinical algorithm for NGS molecular diagnosis of ARCA; the secondary objective is to evaluate if the application of this algorithm coupled with a targeted bioinformatic analysis can increase the diagnostic yield of the NGS analysis.

Conditions

Ataxia

Keywords

Cerebellar ataxia; Neurogenetics; Next generation sequence; Clinical algorithm

Outcome Measures

Primary Outcomes (1)

• Agreement between the prediction of the algorithm and the result of the standard NGS analysis

  In order to validate in clinical practice a semi-automated clinical algorithm designed to guide the molecular diagnosis obtained by Next Generation Sequencing (NGS) in patients with suspected Autosomal Recessive Cerebellar Ataxia (ARCA), we will measure the agreement between the prediction of the algorithm and the result of the standard NGS analysis. For each patient the agreement is defined as: 1) one of the first 5 gene predicted with the highest probability by the algorithm is also the mutated gene found after the NGS analysis; 2) if no gene is predicted by the algorithm (= none of the gene has a prediction score \> 20) and no mutation is found after NGS analyses.

  1 day

Secondary Outcomes (1)

• Percentage of patients for whom the prediction based on the algorithm suggested the right diagnosis, while the standard NGS analysis was not informative

  1 day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adut Patients with suspicion of recessive cerebellar ataxia , with onset before the age of 50 and with negative molecular analisys for Friedreich ataxia and dominant spinocerebellar ataxias due to trinucleotide expansion. .

You may not qualify if:

• \- objecting to the computer processing of the data contained in the medical file.

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Neurology Department, CHU de Strasbourg-France: collaborator
• Genetic Department , CHU Montpellier-France: collaborator

Study Sites (1)

Uh Montpellier

Montpellier, 34295, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Genetic database of approximately 150 patients with cerebellar ataxia, referred since September 2013 for exome analysis to the Montpellier University Hospital Center. The genetic data are from clinical exome capture sequencing with the Trusight One sequencing panel kit (www.illumina.com/trusightone), allowing exploration of approximately 5,000 human disease genes. Each sample is accompanied by a consent that allows genetic analysis and data processing. Each sample is also accompanied by clinical information, usually consisting of a clinical information sheet adapted to patients with genetic ataxias or clinical reports. These data are already accessible.

MeSH Terms

Conditions

Ataxia; Cerebellar Ataxia

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases

Study Officials

• Cecilia Marelli, MD

  University Hospitals of Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 23, 2019
• Study Start: November 1, 2019
• Primary Completion: March 30, 2022
• Study Completion: March 30, 2022
• Last Updated: April 12, 2022

Record last verified: 2022-04

Locations

FR (1)