Mitochondrial Myopathies

The central role of mitochondrial genetics in the elucidation of disorders where energy metabolism is involved has been greatly undervalued in the past. Unfortunately, this has also been the case in South Africa. One of the aims of this project was to address the genetic basis of mitochondrial disorders in the South African population.

Initially patients referred to our national referral centre (launched in the early stages of this programme) we screened for known mutations in their mitochondrial genomes. To this end the mitochondrial DNA (mtDNA) of several patients suspected of harbouring mitochondrial mutations were screened with standardised mutation detection protocols.

However, only the most common mitochondrial mutation (at position 3243) was detected in a single patient. A subsequent phase of this research programme included the screening of the mitochondrial genomes of selected patients for novel changes. Several previous students utilised a sequence-based genome screen for these selected mitochondrial genomes. This effort culminated in the detection of ca. 25 novel changes in this group of South African patients.

After evaluation, some of these novel mutations can be investigated to determine their role in the pathogenesis of mitochondrial disorders. Several strategies to detect mitochondrial alterations have been investigated, and development of the application of a real-time PCR strategy is currently underway.

Unique contributions from this research programme are summarised below:

  • –First comprehensive analysis of the mitochondrial myopathies on the molecular level in South Africa.

Current and previous collaborators were from the following institutions:

  • –Centre for Molecular and Mitochondrial Medicine and Genetics, University of California at Irvine, CA, USA.
  • –Emory University and Mercer University School of Medicine, Macon, GA, U.S.A.
  • –Centre for Genome Research, North-West University.
  • –Biochemistry, North-West University, South Africa.
  • –Department of Paediatrics, University of Pretoria, South Africa.