Mitochondrial Mutations and Hearing Loss

  • Nathan Fischel-Ghodsian

Abstract

Mitochondrial-related hearing loss is not uncommon, can be caused by a number of different mutations, and because of the susceptibility of individuals with the 1555 mutation and their maternal relatives to aminoglycosides is important to diagnose. The role of acquired mitochondrial mutations in presbycusis is suggested at this time, but requires further study for confirmation that the that relationship exists is causal. Lastly, the pathophysiological pathways between the mitochondrial mutations and the hearing impairment are not well understood, and experimental approaches using animal models and a dissection of mitochondrial RNA processing and translation are applied to eventually elucidate these pathways.

Keywords

Toxicity Streptomycin Glycoside Cytosine Myopathy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alcolado J.C., Majid A., Brockington M., Sweeney M.G., Morgan R., Rees, Harding A.E., and Barnett A.H. (1994) Mitochondrial gene defects in patients with NIDDM. Diabetologia 37: 372–376.PubMedCrossRefGoogle Scholar
  2. Arnaudo E., Hirano M., Seelan R.S., Milatovich A., Hsieh C., Fabriscke G.M., Grossman L.I., Francke U., and Schon E.A. (1992) Tissue-specific expression and chromosome assignment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase. Gene 119: 299–305.PubMedCrossRefGoogle Scholar
  3. Attardi G., and Schatz G. (1988) Biogenesis of mitochondria. Annu. Rev. Cell Biol. 4: 289–333.CrossRefGoogle Scholar
  4. Bacino C.M., Prezant T.R., Bu X., Fournier P., and Fischel-Ghodsian N. (1995) Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics 5: 165–172.PubMedCrossRefGoogle Scholar
  5. Ballinger S.W., Shoffner J.M., Hedaya E.V., Trounce I., Polak M.A., Koontz D.A., and Wallace D.C. (1992) Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial deletion. Nature Genetics 1: 11–15.PubMedCrossRefGoogle Scholar
  6. Bindoff L.A., Howell N., Poulton J., McCullough D.A., Morten K.J., Lightowlers R.N., Tùrnbull D.M., and Weber K. (1993) Abnormal RNA processing associated with a novel tRNA mutation in mitochondrial DNA. J. Biol. Chem. 268: 19559–19564.PubMedGoogle Scholar
  7. Braverman I., Jaber L., Levi H., Adelman C., Amos K.S., Fischel-Ghodsian N., Shohat M., and Elidan J. (1996) Audio-vestibular findings in patients with deafness caused by a mitochondrial susceptibility mutation and precipitated by an inherited nuclear mutation or aminoglycosides. Arch. Otolaryngol Head Neck Surg. 122: 1001–1004.CrossRefGoogle Scholar
  8. Bykhovskaya Y., Shohat M., Ehrenman K., Johnson D.E, Hamon M., Cantor R., Aouizerat B., Bu X., Rotter J.I., Jaber L., and Fischel-Ghodsian N. (1998) Evidence for complex nuclear inheritance in a pedigree with non-syndromic deafness due to a homoplasmic mitochondrial mutation. Am. J. Med. Genet. 77: 421–446.PubMedCrossRefGoogle Scholar
  9. Casano R.A.M.S., Bykhovskaya Y., Johnson D.E, Torricelli E, Bigozzi M., and Fischel-Ghodsian N. Hearing loss due to the mitochondrial A1555G mutation in Italian families (submitted).Google Scholar
  10. El-Schahawi M., de Munain L., Sarrazin A.M., Shanske A.L., Basirico M., Shanske S., and DiMauro S. (1997) Two large Spanish pedigrees with non-syndromic sensorineural deafness and the mtDNA mutation at nt 1555 in the 12SrRNA gene: evidence of heteroplasmy. Neurology 48: 453–456.PubMedCrossRefGoogle Scholar
  11. Estivill X., Govea N., Barcelo A., Perello E., Badenas C., Romero E., Moral L., Scozzari R., D’Urbano L., Zeviani M., and Torroni A. (1998) Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment with aminoglycosides. Am. J. Hum. Genet. 62: 27–35.PubMedCrossRefGoogle Scholar
  12. Fischel-Ghodsian N., Prezant T.R., Bu X., and Öztas S. (1993) Mitochondrial ribosomal RNA gene mutation associated with aminoglycoside ototoxicity. Am. J. Otolaryngol 14: 399–403.PubMedCrossRefGoogle Scholar
  13. Fischel-Ghodsian N., Prezant T.R., Fournier P., Stewart I.A., and Maw M. (1995) Mitochondrial tRNA mutation associated with non-syndromic deafness. Am. J. Otolaryngol 16: 403–408.PubMedCrossRefGoogle Scholar
  14. Fischel-Ghodsian N., Bykhovskaya Y., Taylor K., Kahen T., Cantor R., Ehrenman K., Smith R., and Keithley E. (1997a) Temporal bone analysis of patients with presbycusis reveals high frequency of mitochondrial mutations. Hearing Res. 110: 147–154.CrossRefGoogle Scholar
  15. Fischel-Ghodsian N., Prezant T.R., Chaltraw W, Wendt K.A., Nelson R.A., Amos K.S., and Falk R.E. (1997b) Mitochondrial gene mutations: a common predisposing factor in aminoglycoside ototoxicity. Am. J. Otolaryngol 18: 173–178.CrossRefGoogle Scholar
  16. Guan M., Fischel-Ghodsian N., and Attardi G. (1996) Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation. Hum. Molec. Genet. 5: 963–972.Google Scholar
  17. Guan M., Enriquez J.A., Fischel-Ghodsian N., and Attardi G. (1997) Pathogenetic mechanism of the mitochondrial tRNASer(UCN) precursor 7445 mutation and coexisting complex I subunit mtDNA mutations associated with non-syndromic deafness. Am. J. Hum. Genet. 61: A1807.Google Scholar
  18. Hamasaki K., and Rando R.R. (1997) Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness. Biochem. 36: 12323–12328.CrossRefGoogle Scholar
  19. Higashi K. (1989) Unique inheritance of streptomycin-induced deafness. Clin. Genet. 35: 433–436.PubMedCrossRefGoogle Scholar
  20. Howell N. (1994) Mitochondrial gene mutations and human diseases: a prolegomenon. Am. J. Hum. Genet. 55: 219–224.PubMedGoogle Scholar
  21. Hu D.-N., Qui W-Q., Wu B.-T., Fang L.-Z., Gu Y-P., Zhang Q.-H., Yan J.-H., Ding Y-Q., and Wong H. (1991) Genetic aspects of antibiotic induced deafness: mitochondrial inheritance. J. Med. Genet. 28: 79–83.PubMedCrossRefGoogle Scholar
  22. Hutchin T., Haworth I., Higashi K., Fischel-Ghodsian N., Stoneking M., Saha N., Amos C., and Cortopassi G. (1993) A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nucleic Acids Res. 21: 4174–4179.CrossRefGoogle Scholar
  23. Jaber L., Shohat M., Bu X., Fischel-Ghodsian N., Yang H.Y., Wang S.J., and Rotter J.I. (1992) Sensorineural deafness inherited as a tissue specific mitochondrial disorder. J. Med. Genet. 29: 86–90.PubMedCrossRefGoogle Scholar
  24. Kadowaki T., Kadowaki H., Mori Y., Tobe K., Sakuta R., Suzuki Y., Tanabe Y., Sakura H., Awata T., Goto Y-I., Hayakawa T., Matsuota K., Kawamori R., Kamada T., Horai S., Nonaka I., Hagura R., Akanuma Y., and Yazaki Y. (1994) A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. New Engl. J. Med. 330: 962–968.Google Scholar
  25. Katagiri H., Asano T., Ishihara H., Inukai K., Anai M., Yamanouchi T., Tsukuda K., Kikuchi M., Kitaoka H., Ohsawa N., Yazaki Y., and Oka Y. (1994) Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNALeu(UUR) gene mutation in Japanese patients. Diabetologia 37: 504–510.PubMedCrossRefGoogle Scholar
  26. Kobayashi S., Amikura R., and Okada M. (1993) Presence of mitochondrial large ribosomal RNA outside mitochondria in germ plasm of Drosophila melanogaster. Science 260: 1521–1524.PubMedCrossRefGoogle Scholar
  27. Konigsmark B.W., and Gorlin R.J. (1976) Genetic and metabolic deafness. Page 364–365. W.B. Saunders Co.Google Scholar
  28. Nagley P., Zhang C., Martinus R.D., Vaillant E, and Linnane A.W. (1993) Mitochondrial DNA mutations and human aging: Molecular biology, bioenergetics, and redox therapy. In: DiMauro S., and Wallace D.C. (eds). Mitochondrial DNA in human pathology. Raven Press, New York.Google Scholar
  29. Oka Y., Katagiri H., Yazaki Y., Murase T., and Kobayashi T. (1993) Mitochondrial gene mutation in isletcell-antibody-positive patients who were initially non-insulin-dependent diabetics. Lancet 342: 527–528.PubMedCrossRefGoogle Scholar
  30. Pandya A., Xia X., Radnaabazar J., Batsuuri J., Dangaansuren B., Odgerel D., Fischel-Ghodsian N., and Nance W.E. (1997) Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J. Med. Genet. 34: 169–172.PubMedCrossRefGoogle Scholar
  31. Prezant T.R., Agapian J.V., Bohlman M.C., Bu X., Oztas S., Qiu W.Q., Amos K.S., Cortopassi G.A., Jaber L., Rotter J.I., Shohat M., and Fischel-Ghodsian N. (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature Genetics 4: 289–294.PubMedCrossRefGoogle Scholar
  32. Reid F.M., Vernham G.A., and Jacobs H.T. (1994) A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness. Hum. Mut. 3: 243–247.CrossRefGoogle Scholar
  33. Reardon W., Ross R.J.M., Sweeney M.G., Luxon L.M., Pembrey M.E., Harding A.E., and Trembath R.C. (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. Lancet 340: 1376–1379.PubMedCrossRefGoogle Scholar
  34. Sevior K.B., Hatamochi A., Stewart I.A., Bykhovskaya Y., Allen-Powell D.R., Fischel-Ghodsian N., and Maw M. (1998) Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness. Am. J. Med. Genet. 75: 179–185.PubMedCrossRefGoogle Scholar
  35. Stebbins W.C., McGinn C.S., and Feitosa A.G. (1981) Animal models in the study of ototoxic hearing loss, in Lerner S.A., Matz G.L., and Hawkins J.E. jr. (eds): Aminoglycoside Ototoxicity, pp. 5–25. Boston, Little, Brown and Company.Google Scholar
  36. Suomalainen A., Kaukonen J., Timonen R., Haltia M., Weissenbach J., Somer H., and Peltonen L. (1994) Nuclear gene causing multiple mtDNA deletions in autosomal dominant ophthalmoplegia maps to a distinct chromosomal region: involvement of both nuclear and mitochondrial DNA in a single disorder. Am. J. Hum. Genet. 55: 59 (abstract).Google Scholar
  37. Tiranti V., Chariot P., Carella F., Toscano A., Soliveri P., Girlanda P., Carrara F., Fratta G.M., Reid F.M., Mariotti C., and Zeviani M. (1995) Maternally inherited hearing loss, ataxia and myoclonus associated with a novel point mutation in mitochondrial tRNASer(UCN) gene. Hum. Mol. Genet. 4: 1421–1427.Google Scholar
  38. van den Ouweland J.M.W., Lemkes H.H.P.J., Ruitenbeek W., Sandkuijl L.A., De Vijlder M.E, Struyvenberg P.A.A., van de Kamp J.J.P., and Massen J.A. (1992) Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted Type II diabetes mellitus and deafness. Nature Genet. 1: 368–371.PubMedCrossRefGoogle Scholar
  39. Verhoeven K., Ensink R.J.H., Tiranti V., Huygen P., Johnson D.F., Schatteman I., Van Laer L., Verstreken M., Van de Heyning P., Fischel-Ghodsian N., Zeviani M., Cremers C.W.R.J., Willems P.J., and Van Camp G. Different penetrance of neurological symptoms associated with a mutation in the mitochondrial tRNA Ser(UCN) gene (submitted).Google Scholar
  40. Wang C.R., Loveland B.E., and Fischer-Lindahl K. (1991) H-2M3 encodes the MHC class I molecule presenting the maternally transmitted antigen of the mouse. Cell 66: 335–345.PubMedCrossRefGoogle Scholar
  41. Zeviani M. (1992) Nucleus-driven mutations of human mitochondrial DNA. J. Inher. Metab. Dis. 15: 456–471.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic/Plenum Publishers, New York 2000

Authors and Affiliations

  • Nathan Fischel-Ghodsian
    • 1
  1. 1.Ahmanson Department of Pediatrics, Steven Spielberg Pediatric Research CenterCedars-Sinai Medical Center and UCLA School of MedicineLos AngelesUSA

Personalised recommendations