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Mitochondrial D NA Analysis from Exome Sequencing Data Improves Diagnostic Yield in Neurological Diseases
Author(s) -
Poole Olivia V.,
Pizzamiglio Chiara,
Murphy David,
Falabella Micol,
Macken William L.,
Bugiardini Enrico,
Woodward Cathy E.,
Labrum Robyn,
Efthymiou Stephanie,
Salpietro Vincenzo,
Chelban Viorica,
Kaiyrzhanov Rauan,
Maroofian Reza,
Amato Anthony A.,
Gregory Allison,
Hayflick Susan J.,
Jonvik Hallgeir,
Wood Nicholas,
Houlden Henry,
Vandrovcova Jana,
Hanna Michael G.,
Pittman Alan,
Pitceathly Robert D.S.
Publication year - 2021
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26063
Subject(s) - exome sequencing , yield (engineering) , medicine , biology , phenotype , genetics , gene , materials science , metallurgy
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