Nature Genetics
1, 368 - 371 (1992)
doi:10.1038/ng0892-368
Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafnessJ.M.W. van den Ouweland1, H.H.P.J. Lemkes2, W. Ruitenbeek3, L.A. Sandkuijl4, M.F. de Vijlder2, P.A.A. Struyvenberg5, J.J.P. van de Kamp6
& J.A. Maassen1
1Department of Medical Biochemistry, Sylvius Laboratories, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands
2Department of Endocrinology and Metabolic Diseases, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands
3Department of Paediatrics, University Hospital of Nijmegen, Nijmegen, The Netherlands
4Department of Clinical Genetics, University Hospital Dijkzigt, Rotterdam, The Netherlands
5Department of ENT, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands
6Department of Clinical genetics, University Hospital of Leiden, 2300 AL, Leiden, The Netherlands 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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