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Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness

Nature Genetics volume 1, pages 368–371 (1992)Cite this article

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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Authors and Affiliations

  1. Department of Medical Biochemistry, Sylvius Laboratories, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands

    J.M.W. van den Ouweland & J.A. Maassen

  2. Department of Endocrinology and Metabolic Diseases, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands

    H.H.P.J. Lemkes & M.F. de Vijlder

  3. Department of Paediatrics, University Hospital of Nijmegen, Nijmegen, The Netherlands

    W. Ruitenbeek

  4. Department of Clinical Genetics, University Hospital Dijkzigt, Rotterdam, The Netherlands

    L.A. Sandkuijl

  5. Department of ENT, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands

    P.A.A. Struyvenberg

  6. Department of Clinical genetics, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands

    J.J.P. van de Kamp

Authors
  1. J.M.W. van den Ouweland
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  2. H.H.P.J. Lemkes
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  4. L.A. Sandkuijl
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  5. M.F. de Vijlder
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  7. J.J.P. van de Kamp
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  8. J.A. Maassen
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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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