Nature Genetics
1, 11 - 15 (1992)
doi:10.1038/ng0492-11
Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletionScott W. Ballinger1, 2, John M. Shoffner1, 3, Ellis V. Hedaya4, 3, Ian Trounce1, Meraida A. Polak1, 3, Deborah A. Koontz1
& Douglas C. Wallace1, 2, 3
1Departments of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA
2Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
3Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
4Atlanta Neurological Clinic, Atlanta, Georgia 30322, USA Diabetes mellitus (DM) is one of the most common chronic disorders of children and adults. Several reports have suggested an increased incidence of maternal transmission in some forms of DM. Therefore, we tested a pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations and discovered a 10.4 kilobase (kb) mtDNA deletion. This deletion is unique because it is maternally inherited, removes the light strand origin (OL) of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of mtDNA deletion syndromes. This discovery demonstrates that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics.
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