Abstract
Non–insulin–dependent (type II) diabetes mellitus (NIDDM) is characterized by hyperglycaemia and insulin resistance, and affects nearly 5% of the general population. Inherited factors are important for its development, but the genes involved are unknown. We have identified a large pedigree in which NIDDM, in combination with a sensorineural hearing loss, is maternally inherited. The maternal inheritance and the observed decrease in mitochondrial enzyme activities of the respiratory chain indicate a genetic defect in the mitochondrial DNA. An A to G transition was identified at nucleotide 3,243, a conserved position in the mitochondrial gene for tRNALeu(UUR). This mutation cosegregates with the disease in this family and is absent in controls, and indicates that a point mutation in mitochondrial DNA is a pathogenetic factor for NIDDM.
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Barnett, A.H., Eff, C., Leslie, R.D.G. & Pyke, D.A. Diabetologia 20, 87–93 (1981).
Bell, G.I. Diabetes 40, 413–422 (1991).
Moller, D.E., Yokota, A. & Flier, J.S. Diabetes 38, 1496–1500 (1989).
Cama, A. et al. J. clin. endocrinol. Metab. 70, 1155–1161 (1990).
Lekanne Deprez, R.H. et al. Diabetologia 32, 740–744 (1989).
Kusari, J., Verma, U.S., Buse, J.B., Henry, R.R. & Olefsky, J.M. J. clin. Invest. 88, 1323–1330 (1991).
Dörner, G. & Mohnike, A. Endokrinologie 68, 121–124 (1976).
Alcolado, J.C. & Alcolado, R. Br. med. J. 302, 1178–1180 (1991).
Ballinger, S.W. et al. Nature Genet. 1, 11–15 (1992).
Goto, Y., Nonaka, I., Horai, S. Nature 348, 651–653 (1990).
Charles, M.A., Fontbonne, A., Thibult, N., Warnet, J., Rosselin, G.E. & Eschwege, E. Diabetes 40, 796–799 (1991).
Van den Ouweland, J.M.W., Lemkes, H. & Maassen, J.A. Nucleic Acids Res. 19, 1962–1962 (1991).
Anderson, S. et al. Nature 290, 457–465 (1981).
Wallace, D.C. et al. Science 242, 1427–1430 (1988).
Shoffner, J.M., Lott, M.T., Lezza, A.M.S., Seibel, P., Ballinger, S.W. & Wallace, D.C. Cell 61, 931–937 (1990).
Johns, D.R. & Hurko, O. Lancet 337, 927–928 (1991).
Shoffner, J.M. & Wallace, D.C. Adv. hum. Genet. 19, 267–330 (1990).
Goto, Y. et al. Neurology 42, 545–550 (1992).
Ciafaloni, E. et al. Ann. Neurol. 31, 391–398 (1992).
Moraes, C.T., Ricci, E., Bonilla, E., DiMauro, S. & Schon, E.A. Am. J. hum. Genet. 50, 934–949 (1992).
Van den Ouweland, J.M.W. et al. Nucleic Acids Res. 20, 679–682 (1992).
Fischer, J.C. et al. Eur. J. Pediatr. 144, 441–444 (1986).
Miller, S.A., Dykes, D.D. & Polesky, H.F. Nucleic Acids Res. 16, 1215–1215 (1988).
Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular cloning: a Laboratory Manual 2edn (Cold Spring Harbor Laboratory Press, 1989).
Saiki, R.K. et al. Science 239, 487–491 (1988).
Casanova, J.L., Pannetier, C., Jaulin, C. & Kourilsky, P. Nucleic Acids Res. 18, 4028–4028 (1990).
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van den Ouweland, J., Lemkes, H., Ruitenbeek, W. et al. Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1, 368–371 (1992). https://doi.org/10.1038/ng0892-368
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DOI: https://doi.org/10.1038/ng0892-368
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