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Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings
  1. Surita Meldau1,2,
  2. Elizabeth Patricia Owen1,2,
  3. Kashief Khan2,
  4. Gillian Tracy Riordan3,4
  1. 1Division of Chemical Pathology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
  2. 2Chemical Pathology, National Health Laboratory Services, Groote Schuur Hospital, Cape Town, South Africa
  3. 3Division of Paediatric Neurology, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa
  4. 4Red Cross War Memorial Children's Hospital, Cape Town, South Africa
  1. Correspondence to Surita Meldau, Division of Chemical Pathology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town 7925, South Africa; surita.meldau{at}


Aims Mitochondrial diseases form one of the largest groups of inborn errors of metabolism. The birth prevalence is approximately 1/5000 in well-studied populations, but little has been reported from Sub-Saharan Africa. The aim of this study was to describe the genetics underlying mitochondrial disease in South Africa.

Methods An audit was performed on all mitochondrial disease genetic testing performed in Cape Town, South Africa.

Results Of 1614 samples tested for mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) variants in South Africa between 1994 and 2019, there were 155 (9.6 %) positive results. Pathogenic mtDNA variants accounted for 113 (73%)/155, from 96 families. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, 37 (33%)/113, Leber’s hereditary optic neuropathy, 26 (23%)/113, and single large mtDNA deletions, 22 (20%)/113, accounted for 76%. Thirty eight of 42 nDNA-positive results were homozygous for the MPV17 pathogenic variant c.106C>T (p.[Gln36Ter, Ser25Profs*49]) causing infantile neurohepatopathy, one of the largest homozygous groups reported in the literature. The other nDNA variants were in TAZ1, CPT2, BOLA3 and SERAC1. None were identified in SURF1, POLG or PDHA1.

Conclusions Finding a large group with a homozygous nuclear pathogenic variant emphasises the importance of looking for possible founder effects. The absence of other widely described pathogenic nDNA variants in this cohort may be due to reduced prevalence or insufficient testing. As advances in therapeutics develop, it is critical to develop diagnostic platforms on the African subcontinent so that population-specific genetic variations can be identified.

  • DNA
  • medical laboratory science
  • genetic diseases
  • inborn

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  • Handling editor Tahir S Pillay.

  • Contributors SM helped in conceptualisation, planning, conduct and reporting. EPO helped in conceptualisation and conduct. KK helped in conducting the study. GTR helped in conceptualisation, planning and reporting.

  • Funding This study was funded by National Health Laboratory Service.

  • Map disclaimer The depiction of boundaries on the map(s) in this article does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. The map(s) are provided without any warranty of any kind, either express or implied.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the University of Cape Town Human Research Ethics Committee with ref: HREC/REF:024/2018.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Our data are kept on a secure server as part of a diagnostic-linked patient database. It contains sensitive patient information only viewed by laboratory diagnostic staff under strict patient confidentiality agreements. In order to share the data used, it would first need to be deidentified and cleaned up prior to sharing. This can be done upon request, pending additional ethics clearance.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.