@article {Thomas445, author = {Quentin Thomas and Antonio Vitobello and Frederic Tran Mau-Them and Yannis Duffourd and Agn{\`e}s Fromont and Maurice Giroud and Benoit Daubail and Agn{\`e}s Jacquin-Piques and Marie Hervieu-Begue and Thibault Moreau and Guy-Victor Osseby and Philippine Garret and Sophie Nambot and Julian Delanne and Ange-Line Bruel and Arthur Sorlin and Patrick Callier and Anne-Sophie Denomme-Pichon and Laurence Faivre and Yannick B{\'e}jot and Christophe Philippe and Christel Thauvin-Robinet and S{\'e}bastien Moutton}, title = {High efficiency and clinical relevance of exome sequencing in the daily practice of neurogenetics}, volume = {59}, number = {5}, pages = {445--452}, year = {2022}, doi = {10.1136/jmedgenet-2020-107369}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objective To assess the efficiency and relevance of clinical exome sequencing (cES) as a first-tier or second-tier test for the diagnosis of progressive neurological disorders in the daily practice of Neurology and Genetic Departments.Methods Sixty-seven probands with various progressive neurological disorders (cerebellar ataxias, neuromuscular disorders, spastic paraplegias, movement disorders and individuals with complex phenotypes labelled {\textquoteleft}other{\textquoteright}) were recruited over a 4-year period regardless of their age, gender, familial history and clinical framework. Individuals could have had prior genetic tests as long as it was not cES. cES was performed in a proband-only (60/67) or trio (7/67) strategy depending on available samples and was analysed with an in-house pipeline including software for CNV and mitochondrial-DNA variant detection.Results In 29/67 individuals, cES identified clearly pathogenic variants leading to a 43\% positive yield. When performed as a first-tier test, cES identified pathogenic variants for 53\% of individuals (10/19). Difficult cases were solved including double diagnoses within a kindred or identification of a neurodegeneration with brain iron accumulation in a patient with encephalopathy of suspected mitochondrial origin.Conclusion This study shows that cES is a powerful tool for the daily practice of neurogenetics offering an efficient (43\%) and appropriate approach for clinically and genetically complex and heterogeneous disorders.All data relevant to the study are included in the article or uploaded as online supplemental information.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/59/5/445}, eprint = {https://jmg.bmj.com/content/59/5/445.full.pdf}, journal = {Journal of Medical Genetics} }