NOVEL MITOCHONDRIAL-DNA MUTATION IN TRNA(LYS) (8296A-]G) ASSOCIATED WITH DIABETES

Mutation in the mitochondrial gene at position 3243 was recently ident ified in a large pedigree of diabetes mellitus and deafness. As the mi tochondria play an important role in glucose-stimulated insulin secret ion in pancreatic beta-cells, we therefore searched for such mutations to detect a candidate gene for diabetes. We screened 10 diabetic subj ects with clinical features suggesting mitochondrial DNA mutations, An adenine to guanine point mutation in tRNA(Lys) in at position 8296 (t he 8296 mutation) was newly identified. Subsequently, we screened 1216 diabetic subjects, 44 patients with sensorineural deafness subjects a nd 300 non-diabetic control subjects for this mutation. We identified the mutation in 11 (0.90%) unrelated diabetic subjects, one (2.3%) pat ient with deafness and no non-diabetic control subject. Seven of these 12 subjects showed maternal inheritance. Deafness was seen in 7 of 12 probands, Four family pedigrees showed maternal inheritance of diabet es over two or three generations, Subjects carrying the 8296 mutation may develop diabetes and the mutation can explain as high as ca. 1% of the causes of diabetes. (C) 1998 Academic Press.