Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA.

Family studies of diabetes mellitus (DM) show that patients are more likely to have affected mothers than affected fathers. Since the inheritance of mitochondrial (mtDNA), unlike nuclear DNA, is exclusively maternal, could it be that defect(s) in mtDNA account for some cases of DM? Such defects have been associated with rare neurological syndromes, in some of which DM has been an accompanying feature. We have looked for glucose intolerance and for a previously known point mutation of mtDNA in a family, some of whose members have a multisystem disorder with DM but not neurological involvement. DNA samples were obtained from fourteen family members. The point mutation (affecting position 3243 in the tRNA leucine mitochondrial gene) was found in all three diabetic patients and post mortem tissues in the proband; it was also found in seven offspring of female patients. It was not found in the two children of the male proband. The contribution of this mutation to DM in general is not known but clinicians ought to be aware of the possibility, especially in families with multisystem disease and maternal transmission.