Mitochondrial DNA analysis from exome sequencing data improves the diagnostic yield in neurological diseases

Olivia V Poole, Chiara Pizzamiglio, David Murphy, Micol Falabella, William L Macken, Enrico Bugiardini, Cathy E Woodward, Robyn Labrum, Stephanie Efthymiou, Vincenzo Salpietro, Viorica Chelban, Rauan Kaiyrzhanov, Reza Maroofian, Anthony A Amato, Allison Gregory, Susan J Hayflick, Queen Square Genomics, Hallgeir Jonvik, Nicholas Wood, Henry Houlden, Jana Vandrovcova, Michael G Hanna, Alan Pittman, Robert D S Pitceathly
Annals of Neurology 2021 March 11
A rapidly expanding catalogue 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. This article is protected by copyright. All rights reserved.

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