@article{9df00dde68fa49f4b79a6bc21ec6f1a0,
title = "Mitochondrial DNA Analysis from Exome Sequencing Data Improves Diagnostic Yield in Neurological Diseases",
abstract = "A rapidly expanding catalog of neurogenetic disorders has encouraged a diagnostic shift towards early clinical whole exome sequencing (WES). Adult primary mitochondrial diseases (PMDs) frequently exhibit neurological manifestations that overlap with other nervous system disorders. However, mitochondrial DNA (mtDNA) is not routinely analyzed in standard clinical WES bioinformatic pipelines. We reanalyzed 11,424 exomes, enriched with neurological diseases, for pathogenic mtDNA variants. Twenty-four different mtDNA mutations were detected in 64 exomes, 11 of which were considered disease causing based on the associated clinical phenotypes. These findings highlight the diagnostic uplifts gained by analyzing mtDNA from WES data in neurological diseases. ANN NEUROL 2021;89:1240–1247.",
author = "{the SYNaPS Study Group} and {Queen Square Genomics} and Poole, {Olivia V.} and Chiara Pizzamiglio and David Murphy and Micol Falabella and Macken, {William L.} and Enrico Bugiardini and Woodward, {Cathy E.} and Robyn Labrum and Stephanie Efthymiou and Vincenzo Salpietro and Viorica Chelban and Rauan Kaiyrzhanov and Reza Maroofian and Amato, {Anthony A.} and Allison Gregory and Hayflick, {Susan J.} and Hallgeir Jonvik and Nicholas Wood and Henry Houlden and Jana Vandrovcova and Hanna, {Michael G.} and Alan Pittman and Pitceathly, {Robert D.S.} and Issam Alkhawaja and Selina Banu and Maria Bonsignore and Marianthi Breza and {Di Rosa}, Gabriella and Morteza Heidari and Georgios Koutsis and {van den Maagdenberg}, {Arn M.J.M.} and Alfons Macaya and Alexander M{\"u}nchau and Carmela Scuderi and Nazira Zharkinbekova",
note = "Funding Information: This research was conducted as part of the Queen Square Genomics Group at University College London, supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The University College London Hospitals/University College London Queen Square Institute of Neurology sequencing facility receives a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. The clinical and diagnostic “Rare Mitochondrial Disorders” Service in London is funded by the UK NHS Highly Specialized Commissioners. R.D.S.P. and M.F. are supported by a Medical Research Council (UK) Clinician Scientist Fellowship (MR/S002065/1). R.D.S.P., M.G.H., H.H., J.V., H.J., and W.L.M. receive funding from a Medical Research Council (UK) strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) (MR/S005021/1). J.V. holds a fellowship from the Health Education England Genomics Education Programme. V.C. is funded by the Association of British Neurologists/Multiple System Atrophy Trust Clinical Research Training Fellowship. H.H. is grateful to the Medical Research Council (UK), the Wellcome Trust Synaptopathies Award, Ataxia UK, Rosetrees Trust, Brain Research UK, University College London Official Development Assistance and Low and Middle Income Country award, The Multiple System Atrophy Trust, Muscular Dystrophy UK, and Muscular Dystrophy Association. Publisher Copyright: {\textcopyright} 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",
year = "2021",
month = jun,
doi = "10.1002/ana.26063",
language = "English (US)",
volume = "89",
pages = "1240--1247",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "6",
}