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Mitochondrial DNA Analysis from Exome Sequencing Data Improves Diagnostic Yield in Neurological Diseases.

Olivia V PooleChiara PizzamiglioDavid MurphyMicol FalabellaWilliam L MackenEnrico BugiardiniCathy E WoodwardRobyn LabrumStephanie EfthymiouVincenzo SalpietroViorica ChelbanRauan KaiyrzhanovReza Maroofiannull nullAnthony A AmatoAllison GregorySusan J Hayflicknull nullHallgeir JonvikNicholas W WoodHenry HouldenJana VandrovcovaMichael G HannaAlan PittmanRobert D S Pitceathly
Published in: Annals of neurology (2021)
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.
Keyphrases
  • mitochondrial dna
  • copy number
  • genome wide
  • dna methylation
  • electronic health record
  • oxidative stress
  • big data
  • machine learning
  • gene expression
  • subarachnoid hemorrhage
  • neural network