Validation of a Clinical Algorithm for the Diagnosis of Recessive Ataxias (BASE-AAR)
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|ClinicalTrials.gov Identifier: NCT04099914|
Recruitment Status : Completed
First Posted : September 23, 2019
Last Update Posted : April 12, 2022
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.
|Condition or disease|
|Study Type :||Observational|
|Actual Enrollment :||150 participants|
|Official Title:||Exploitation of a BAse of Genetic Data (Obtained by Next Generation SEquencing) for the Validation of a Clinical Algorithm for the Diagnosis of Recessive Cerebellar Ataxias|
|Actual Study Start Date :||November 1, 2019|
|Actual Primary Completion Date :||March 30, 2022|
|Actual Study Completion Date :||March 30, 2022|
- Agreement between the prediction of the algorithm and the result of the standard NGS analysis [ Time Frame: 1 day ]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.
- Percentage of patients for whom the prediction based on the algorithm suggested the right diagnosis, while the standard NGS analysis was not informative [ Time Frame: 1 day ]The secondary objective is to evaluate whether the application of this algorithm, coupled with a targeted bioinformatic analysis, changes the diagnostic yield compared to a NGS analysis performed in a conventional manner. Therefore, the secondary outcome will be the percentage of patients for whom the prediction based on the algorithm suggested the corrected diagnosis (confirmed in a second time after the review of the genetic data derived from NGS after the application of a targeted bioinformatic analysis), while the standard NGS analysis (blinded to algorithm prediction) was not informative
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04099914
|Montpellier, France, 34295|
|Principal Investigator:||Cecilia Marelli, MD||University Hospitals of Montpellier|