RT Journal Article
SR Electronic
T1 High efficiency and clinical relevance of exome sequencing in the daily practice of neurogenetics
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 445
OP 452
DO 10.1136/jmedgenet-2020-107369
VO 59
IS 5
A1 Quentin Thomas
A1 Antonio Vitobello
A1 Frederic Tran Mau-Them
A1 Yannis Duffourd
A1 Agnès Fromont
A1 Maurice Giroud
A1 Benoit Daubail
A1 Agnès Jacquin-Piques
A1 Marie Hervieu-Begue
A1 Thibault Moreau
A1 Guy-Victor Osseby
A1 Philippine Garret
A1 Sophie Nambot
A1 Julian Delanne
A1 Ange-Line Bruel
A1 Arthur Sorlin
A1 Patrick Callier
A1 Anne-Sophie Denomme-Pichon
A1 Laurence Faivre
A1 Yannick Béjot
A1 Christophe Philippe
A1 Christel Thauvin-Robinet
A1 Sébastien Moutton
YR 2022
UL http://jmg.bmj.com/content/59/5/445.abstract
AB 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 ‘other’) 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.