Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases

Martial Mallaret; Mathilde Renaud; Claire Redin; Nathalie Drouot; Jean Muller; Francois Severac; Jean Louis Mandel; Wahiba Hamza; Traki Benhassine; Lamia Ali-Pacha; Meriem Tazir; Alexandra Durr; Marie-Lorraine Monin; Cyril Mignot; Perrine Charles; Lionel Van Maldergem; Ludivine Chamard; Christel Thauvin-Robinet; Vincent Laugel; Lydie Burglen; Patrick Calvas; Marie-Céline Fleury; Christine Tranchant; Mathieu Anheim; Michel Koenig

doi:10.1007/s00415-016-8112-5

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Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases

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Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases

Martial Mallaret, Mathilde Renaud, Claire Redin, Nathalie Drouot, Jean Muller, Francois Severac, Jean Louis Mandel, Wahiba Hamza, Traki Benhassine, Lamia Ali-Pacha, …

Journal of neurology, Vol.263(7), pp.1314-1322

07/2016

DOI: https://doi.org/10.1007/s00415-016-8112-5

PMID: 27142713

Résumé

Adolescent

Adult

Age of Onset

Aged

Algorithms

Cerebellar Ataxia - diagnosis

Cerebellar Ataxia - genetics

Databases, Genetic

Female

Genes, Recessive - genetics

High-Throughput Nucleotide Sequencing

Humans

Male

Middle Aged

Reproducibility of Results

Retrospective Studies

Young Adult

Establishing a molecular diagnosis of autosomal recessive cerebellar ataxias (ARCA) is challenging due to phenotype and genotype heterogeneity. We report the validation of a previously published clinical practice-based algorithm to diagnose ARCA. Two assessors performed a blind analysis to determine the most probable mutated gene based on comprehensive clinical and paraclinical data, without knowing the molecular diagnosis of 23 patients diagnosed by targeted capture of 57 ataxia genes and high-throughput sequencing coming from a 145 patients series. The correct gene was predicted in 61 and 78 % of the cases by the two assessors, respectively. There was a high inter-rater agreement [K = 0.85 (0.55-0.98) p < 0.001] confirming the algorithm's reproducibility. Phenotyping patients with proper clinical examination, imaging, biochemical investigations and nerve conduction studies remain crucial for the guidance of molecular analysis and to interpret next generation sequencing results. The proposed algorithm should be helpful for diagnosing ARCA in clinical practice.

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Détails

Titre: Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases
Créateurs - sans rôle: Martial Mallaret - Department of Neurology, Movement Disorders Unit, Hôpital de Hautepierre, 67098, Strasbourg cedex, France
Mathilde Renaud - Université de Strasbourg
Claire Redin - Institut de génétique et de biologie moléculaire et cellulaire
Nathalie Drouot - Institut de génétique et de biologie moléculaire et cellulaire
Jean Muller - Laboratoire de Génétique Médicale, UMR_S INSERM U1112, IGMA, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
Francois Severac - Hôpitaux Universitaires de Strasbourg
Jean Louis Mandel - Chaire de Génétique Humaine, Collège de France, Illkirch, France
Wahiba Hamza - Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, USTHB, Algiers, Algeria
Traki Benhassine - Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, USTHB, Algiers, Algeria
Lamia Ali-Pacha - Département de Neurologie, Centre hospitalier universitaire Mustapha Pacha, Algiers, Algeria
Meriem Tazir - Laboratoire de Neurosciences, Université d'Alger, Algiers, Algeria
Alexandra Durr - Institut du Cerveau
Marie-Lorraine Monin - Département de Génétique et de Cytogénétique, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013, Paris, France
Cyril Mignot - Assistance Publique – Hôpitaux de Paris
Perrine Charles - Assistance Publique – Hôpitaux de Paris
Lionel Van Maldergem - Centre de Génétique Humaine, Université de Franche-Comté, Besançon, France
Ludivine Chamard - Research Memory Center (CMRR), CHU Besançon, Besançon, France
Christel Thauvin-Robinet - Centre de Génétique, Hôpital d'Enfants, CHU Dijon and EA4271, Université de Bourgogne, Dijon, France
Vincent Laugel - Hôpitaux Universitaires de Strasbourg
Lydie Burglen - Assistance Publique – Hôpitaux de Paris
Patrick Calvas - Service de Génétique Médicale, Pavillon Ch Lefebvre, Hôpital Purpan-CHU de Toulouse, TSA 40031, 31059, Toulouse Cedex, France
Marie-Céline Fleury - Department of Neurology, Movement Disorders Unit, Hôpital de Hautepierre, 67098, Strasbourg cedex, France
Christine Tranchant - Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
Mathieu Anheim - Université de Strasbourg
Michel Koenig - Université de Montpellier
Détails de publication: Journal of neurology, Vol.263(7), pp.1314-1322
Identifiants: 99158872709311
Unité académique: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Langue: English
Type de ressource: Journal article