Mitochondrial DNA Mutations and Diabetes: Another Step toward Individualized Medicine
Authors: Nathan Fischel-Ghodsian
Journal: Annals of Internal Medicine (2001)

Editorials1 May 2001Mitochondrial DNA Mutations and Diabetes: Another Step toward Individualized MedicineNathan Fischel-Ghodsian, MDNathan Fischel-Ghodsian, MDDr. Fischel-Ghodsian: Cedars-Sinai Medical Center; Los Angeles, CA 90048Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-9_Part_1-200105010-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Twenty years ago, the mitochondrial chromosome was completely sequenced and the functions of all its genes were identified (1). Those genes code for 13 polypeptides, which are part of the more than 60 polypeptides that form the oxidative phosphorylation and adenosine triphosphate synthetase protein complexes in the inner membrane of the mitochondria. In addition, the mitochondrial chromosome codes for two ribosomal RNAs and 22 transfer RNAs, which participate in the translation of the 13 polypeptides on the mitochondrial ribosomes. Each cell contains hundreds of these chromosomes, and they are transmitted only through the ovum, leading to a maternal inheritance pattern. ...References1. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al . Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457-65. [PMID: 7219534] CrossrefMedlineGoogle Scholar2. Ballinger SW, Shoffner JM, Hedaya EV, Trounce I, Polak MA, Koontz DA, et al . Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion. Nat Genet. 1992;1:11-5. [PMID: 1301992] CrossrefMedlineGoogle Scholar3. Reardon W, Ross RJ, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, et al . Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. Lancet. 1992;340:1376-9. [PMID: 1360090] CrossrefMedlineGoogle Scholar4. van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, et al . Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet. 1992;1:368-71. [PMID: 1284550] CrossrefMedlineGoogle Scholar5. Dorner G, Plagemann A, Reinagel H. Familial diabetes aggregation in type I diabetics: gestational diabetes an apparent risk factor for increased diabetes susceptibility in the offspring. Exp Clin Endocrinol. 1987;89:84-90. [PMID: 3595734] CrossrefMedlineGoogle Scholar6. Pettitt DJ, Aleck KA, Baird HR, Carraher MJ, Bennett PH, Knowler WC. Congenital susceptibility to NIDDM. Role of intrauterine environment. Diabetes. 1988;37:622-8. [PMID: 3360218] CrossrefMedlineGoogle Scholar7. Thomas F, Balkau B, Vauzelle-Kervroedan F, Papoz L. Maternal effect and familial aggregation in NIDDM. The CODIAB Study. CODIAB-INSERM-ZENECA Study Group. Diabetes. 1994;43:63-7. [PMID: 8262318] CrossrefMedlineGoogle Scholar8. Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care. 1998;21 Suppl 2 B142-9. [PMID: 9704242] MedlineGoogle Scholar9. Dabelea D, Knowler WC, Pettitt DJ. Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians. J Matern Fetal Med. 2000;9:83-8. [PMID: 10757442] CrossrefMedlineGoogle Scholar10. Guillausseau PJ, Massin P, Dubois-LaForgue D, Timsit J, Virally M, Gin H, et al . Maternally inherited diabetes and deafness: a multicenter study. Ann Intern Med. 2001;134:721-8. LinkGoogle Scholar11. Fischel-Ghodsian N. Mitochondrial deafness mutations reviewed. Hum Mutat. 1999;13:261-70. [PMID: 10220138] CrossrefMedlineGoogle Scholar12. Kadowaki T, Kadowaki H, Mori Y, Tobe K, Sakuta R, Suzuki Y, et al . A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med. 1994;330:962-8. [PMID: 8121460] CrossrefMedlineGoogle Scholar13. Fischel-Ghodsian N. Homoplasmic mitochondrial DNA diseases as the paradigm to understand the tissue specificity and variable clinical severity of mitochondrial disorders. Mol Genet Metab. 2000;71:93-9. [PMID: 11001802] CrossrefMedlineGoogle Scholar14. Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, et al . Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet. 1993;4:289-94. [PMID: 7689389] CrossrefMedlineGoogle Scholar15. Bykhovskaya Y, Estivill X, Taylor K, Hang T, Hamon M, Casano RA, et al . Candidate locus for a nuclear modifier gene for maternally inherited deafness. Am J Hum Genet. 2000;66:1905-10. [PMID: 10788333] CrossrefMedlineGoogle Scholar16. Johnson KR, Zheng QY, Bykhovskaya Y, Spirina O, Fischel-Ghodsian N. A nuclear-mitochondrial DNA interaction affecting hearing impairment in mice. Nat Genet. 2001;27:191-4. [PMID: 11175788] CrossrefMedlineGoogle Scholar17. Wang CR, Loveland BE, Lindahl KF. H-2M3 encodes the MHC class I molecule presenting the maternally transmitted antigen of the mouse. Cell. 1991;66:335-45. [PMID: 1855254] CrossrefMedlineGoogle Scholar18. Kobayashi S, Amikura R, Okada M. Presence of mitochondrial large ribosomal RNA outside mitochondria in germ plasm of Drosophila melanogaster . Science. 1993;260:1521-4. [PMID: 7684857] CrossrefMedlineGoogle Scholar19. Rimoin DL. Genetics of diabetes mellitus. Diabetes. 1967;16:346-51. [PMID: 5336896] CrossrefMedlineGoogle Scholar20. Raffel LJ, Scheuner MT, Rimoin DL, Rotter JI. Diabetes mellitus.. In: Rimoin DL, Connor JM, Pyeritz RE, eds. Emery and Rimoin's Principles and Practice of Medical Genetics, 3rd ed. New York: Churchill Livingstone; 1996:1401-40. Google Scholar Author, Article, and Disclosure InformationAuthors: Nathan Fischel-Ghodsian, MDAffiliations: Dr. Fischel-Ghodsian: Cedars-Sinai Medical Center; Los Angeles, CA 90048Acknowledgment: The author thanks Drs. Leslie Raffel, Ricardo Perfetti, and Jerome Rotter for their comments on the editorial.Grant Support: By the National Institutes of Health/National Institute on Deafness and Other Communication Disorders (RO1DC01402 and RO1DC04092).Corresponding Author: Nathan Fischel-Ghodsian, MD, Department of Pediatrics, Suite 1165WT, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMaternally Inherited Diabetes and Deafness: A Multicenter Study Pierre-Jean Guillausseau , Pascale Massin , Danièle Dubois-LaForgue , José Timsit , Marie Virally , Henri Gin , Eric Bertin , Jean-Frédéric Blickle , Béatrice Bouhanick , Juliette Cahen , Sophie Caillat-Zucman , Guillaume Charpentier , Pierre Chedin , Christèle Derrien , Pierre-Henri Ducluzeau , André Grimaldi , Bruno Guerci , Edgar Kaloustian , Arnaud Murat , Frédérique Olivier , Michel Paques , Véronique Paquis-Flucklinger , Béatrice Porokhov , Julien Samuel-Lajeunesse , and Bernard Vialettes Maternally Inherited Diabetes and Deafness: A Multicenter Study Pierre-Jean Guillausseau , Pascale Massin , Danièle Dubois-LaForgue , José Timsit , Marie Virally , Henri Gin , Eric Bertin , Jean-Frédéric Blickle , Béatrice Bouhanick , Juliette Cahen , Sophie Caillat-Zucman , Guillaume Charpentier , Pierre Chedin , Christèle Derrien , Pierre-Henri Ducluzeau , André Grimaldi , Bruno Guerci , Edgar Kaloustian , Arnaud Murat , Frédérique Olivier , Michel Paques , Véronique Paquis-Flucklinger , Béatrice Porokhov , Julien Samuel-Lajeunesse , and Bernard Vialettes Metrics Cited byIndividualized medicine, health medicine, and constitutional theory in Chinese medicinemt-Nd2 Allele of the ALR/Lt mouse confers resistance against both chemically induced and autoimmune diabetesMitochondrial DiseasesTowards Integrative postmodern individualized medicine in terms of hierarchic emergenceHereditäre NierenerkrankungenDevelopment of lipophilic cations as therapies for disorders due to mitochondrial dysfunctionHereditäre Nierenerkrankungen 1 May 2001Volume 134, Issue 9_Part_1Page: 777-779KeywordsBlood cellsChromosomesDeafnessHearingInsulin secretionMitochondrial DNAMutationPhenotypesPolypeptidesType 2 diabetes ePublished: 1 May 2001 Issue Published: 1 May 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. 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