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

Abstract : 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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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01405178
Contributeur : Gad - Université de Bourgogne <>
Soumis le : mardi 29 novembre 2016 - 16:01:38
Dernière modification le : samedi 29 juin 2019 - 01:41:57

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Martial Mallaret, Mathilde Renaud, Claire Redin, Nathalie Drouot, Jean Muller, et al.. Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases. Journal of Neurology, Springer Verlag, 2016, 263 (7), pp.1314 - 1322. ⟨http://link.springer.com/article/10.1007%2Fs00415-016-8112-5⟩. ⟨10.1007/s00415-016-8112-5⟩. ⟨hal-01405178⟩

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