Biochemical and molecular diagnosis of mitochondrial respiratory chain disorders

David R. Thorburn, Canny Sugiana, Renato Salemi, Denise M. Kirby, Lisa Worgan, Akira Ohtake, Michael T. Ryan

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84 Citations (Scopus)

Abstract

Biochemical diagnosis of mitochondrial respiratory chain disorders requires caution to avoid misdiagnosis of secondary enzyme defects, and can be improved by the use of conservative diagnostic criteria. Pathogenic mutations causing mitochondrial disorders have now been identified in more than 30 mitochondrial DNA (mtDNA) genes encoding respiratory chain subunits, ribosomal- and t-RNAs. mtDNA mutations appear to be responsible for most adult patients with mitochondrial disease and approximately a quarter of paediatric patients. A family history suggesting maternal inheritance is the exception rather than the norm for children with mtDNA mutations, many of whom have de novo mutations. Prenatal diagnosis and pre-implantation genetic diagnosis can be offered to some women at risk of transmitting a mtDNA mutation, particularly those at lower recurrence risk. Mutations in more than 30 nuclear genes, including those encoding for respiratory chain subunits and assembly factors, have now been shown to cause mitochondrial disorders, creating difficulties in prioritising which genes should be studied by mutation analysis in individual patients. A number of approaches offer promise to guide the choice of candidate genes, including Blue Native-PAGE immunoblotting and microarray expression analysis.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1659
Issue number2-3
DOIs
Publication statusPublished - 6 Dec 2004
Externally publishedYes

Keywords

  • Assembly
  • Microarray
  • Mitochondrial diseases
  • mtDNA
  • Mutation
  • Respiratory chain

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