Neuromuscular Disorders
Volume 20, Issue 2 , Pages 131-135 , February 2010

A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy

  • Charlotte L. Alston

      Affiliations

    • Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK
    • ,
  • Monika Morak

      Affiliations

    • University Hospital of the Ludwig-Maximilians-University, Campus Innenstadt, Munich, Germany
    • MGZ – Center of Medical Genetics, Munich, Germany
    • ,
  • Christopher Reid

      Affiliations

    • Department of Paediatric Nephrology, Evelina Children’s Hospital, Guys & St. Thomas’ NHS Foundation Trust, London, UK
    • ,
  • Iain P. Hargreaves

      Affiliations

    • Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
    • ,
  • Simon A.S. Pope

      Affiliations

    • Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
    • ,
  • John M. Land

      Affiliations

    • Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
    • ,
  • Simon J. Heales

      Affiliations

    • Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
    • Chemical Pathology, Great Ormond Street Hospital, London, UK
    • ,
  • Rita Horvath

      Affiliations

    • Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK
    • ,
  • Helen Mundy

      Affiliations

    • Centre for Inherited Metabolic Disease, Guys & St. Thomas’ NHS Foundation Trust, London, UK
    • ,
  • Robert W. Taylor

      Affiliations

    • Mitochondrial Research Group and NCG Rare Mitochondrial Disorders of Adults and Children Service, Newcastle University, Newcastle upon Tyne, UK
    • Corresponding Author InformationCorresponding author. Address: Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Tel.: +44 191 2223685; fax: +44 191 2824373.

Received 20 July 2009 ,Revised 23 October 2009 ,Accepted 26 October 2009.

References 

  1. Distelmaier F, Koopman WJ, van den Heuvel LP, et al. Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain. 2009;132:833–842
  2. Lazarou M, Thorburn DR, Ryan MT, McKenzie M. Assembly of mitochondrial complex I and defects in disease. Biochim Biophys Acta. 2009;1793:78–88
  3. Sugiana C, Pagliarini DJ, McKenzie M, et al. Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. Am J Hum Genet. 2008;83:468–478
  4. Kirby DM, Kahler SG, Freckmann ML, Reddihough D, Thorburn DR. Leigh disease caused by the mitochondrial DNA G14459A mutation in unrelated families. Ann Neurol. 2000;48:102–104
  5. Kirby DM, Boneh A, Chow CW, et al. Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh’s disease. Ann Neurol. 2003;54:473–478
  6. Lebon S, Chol M, Benit P, et al. Recurrent de novo mitochondrial DNA mutations in respiratory chain deficiency. J Med Genet. 2003;40:896–899
  7. Ugalde C, Triepels RH, Coenen MJ, et al. Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene. Ann Neurol. 2003;54:665–669
  8. McFarland R, Kirby DM, Fowler KJ, et al. De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency. Ann Neurol. 2004;55:58–64
  9. Sarzi E, Brown MD, Lebon S, et al. A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia. Am J Med Genet. 2007;143:33–41
  10. Kirby DM, McFarland R, Ohtake A, et al. Mutations of the mitochondrial ND1 gene as a cause of MELAS. J Med Genet. 2004;41:784–789
  11. Oppenheim ML, Hargreaves IP, Pope S, Land JM, Heales SJ. Mitochondrial cytochrome c release: a factor to consider in mitochondrial disease?. J Inherit Metab Dis. 2009;32:269–273
  12. Taylor RW, Barron MJ, Borthwick GM, et al. Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest. 2003;112:1351–1360
  13. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet. 1999;23:147
  14. Wittig I, Karas M, Schägger H. High resolution clear native electrophoresis for in-gel functional assays and fluorescence studies of membrane protein complexes. Mol Cell Proteomics. 2007;6:1215–1225
  15. Chol M, Lebon S, Bénit P, et al. The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency. J Med Genet. 2003;40:188–191
  16. Shanske S, Coku J, Lu J, et al. The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases. Arch Neurol. 2008;65:368–372
  17. Valente L, Piga D, Lamantea E, et al. Identification of novel mutations in five patients with mitochondrial encephalomyopathy. Biochim Biophys Acta. 2009;1787:491–501
  18. Moslemi AR, Darin N, Tulinius M, Wiklund LM, Holme E, Oldfors A. Progressive encephalopathy and complex I deficiency associated with mutations in MTND1. Neuropediatrics. 2008;39:24–28
  19. Martín-Hernández E, García-Silva MT, Vara J, et al. Renal pathology in children with mitochondrial diseases. Pediatr Nephrol. 2005;20:1299–1305
  20. Hall AM, Unwin RJ, Hanna MG, Duchen MR. Renal function and mitochondrial cytopathy (MC): more questions than answers?. QJM. 2008;101:755–766
  21. Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM. Sequence variation in mitochondrial complex I genes: mutation or polymorphism?. J Med Genet. 2006;43:175–179
  22. Ingman M, Gyllensten U. MtDB: human mitochondrial genome database, a resource for population genetics and medical sciences. Nucleic Acids Res. 2006;34:D749–D751
  23. Downham E, Winterthun S, Nakkestad HL, et al. A novel mitochondrial ND5 (MTND5) gene mutation giving isolated exercise intolerance. Neuromuscul Disord. 2008;18:310–314

PII: S0960-8966(09)00663-4

doi: 10.1016/j.nmd.2009.10.010

Neuromuscular Disorders
Volume 20, Issue 2 , Pages 131-135 , February 2010

Article Tools

* Image Usage & Resolution