title: Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease.
abstract: OBJECTIVE
  The prevalence of mitochondrial disease has proven difficult to establish, predominantly as a result of clinical and genetic heterogeneity. The phenotypic spectrum of mitochondrial disease has expanded significantly since the original reports that associated classic clinical syndromes with mitochondrial DNA (mtDNA) rearrangements and point mutations. The revolution in genetic technologies has allowed interrogation of the nuclear genome in a manner that has dramatically improved the diagnosis of mitochondrial disorders. We comprehensively assessed the prevalence of all forms of adult mitochondrial disease to include pathogenic mutations in both nuclear and mtDNA.
  
  
  METHODS
  Adults with suspected mitochondrial disease in the North East of England were referred to a single neurology center from 1990 to 2014. For the midyear period of 2011, we evaluated the minimum prevalence of symptomatic nuclear DNA mutations and symptomatic and asymptomatic mtDNA mutations causing mitochondrial diseases.
  
  
  RESULTS
  The minimum prevalence rate for mtDNA mutations was 1 in 5,000 (20 per 100,000), comparable with our previously published prevalence rates. In this population, nuclear mutations were responsible for clinically overt adult mitochondrial disease in 2.9 per 100,000 adults.
  
  
  CONCLUSIONS
  Combined, our data confirm that the total prevalence of adult mitochondrial disease, including pathogenic mutations of both the mitochondrial and nuclear genomes (≈1 in 4,300), is among the commonest adult forms of inherited neurological disorders. These figures hold important implications for the evaluation of interventions, provision of evidence-based health policies, and planning of future services.
authors: Wellcome Centre for Mitochondrial Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Institute of Neuroscience, Henry Wellcome Building for Neuroecology, Newcastle upon Tyne, United Kingdom.
authors: Gráinne S
authors: GS
authors: Gorman
authors: Andrew M
authors: AM
authors: Schaefer
authors: Yi
authors: Y
authors: Ng
authors: Nicholas
authors: N
authors: Gomez
authors: Emma L
authors: EL
authors: Blakely
authors: Charlotte L
authors: CL
authors: Alston
authors: Catherine
authors: C
authors: Feeney
authors: Rita
authors: R
authors: Horvath
authors: Patrick
authors: P
authors: Yu-Wai-Man
authors: Patrick F
authors: PF
authors: Chinnery
authors: Robert W
authors: RW
authors: Taylor
authors: Douglass M
authors: DM
authors: Turnbull
authors: Robert
authors: R
authors: McFarland
mesh_terms: D000328:Adult; D002467:Cell Nucleus / Q000235:genetics*; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D004739:England / Q000453:epidemiology; D006801:Humans; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015995:Prevalence; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
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