MITOCHONDRIAL-DNA POINT MUTATION AT NUCLEOTIDE-PAIR-3316 IN A JAPANESE FAMILY WITH HETEROGENEOUS PHENOTYPES OF DIABETES

A mitochondrial DNA (mtDNA) paint mutation at nucleotide pair (np) 331 6 has been reported in relation to diabetes. We recently encountered a non-obese family with this type of mutation. The proband in the affec ted family, a 49-year-old woman who had been previously diagnosed as h aving an insulin-requiring non-insulin-dependent diabetes mellitus (NI DDM), was referred to our hospital for treatment of diabetic gangrene in her left foot. Her insulin secretary capacity was markedly reduced, but the insulin sensitivity evaluated by the euglycemic hyperinsuline mic clamp technique was normal. In addition, her serum lactate level w as markedly increased after a 5 min ambulation, although her serum pyr uvate and ketones remained within the normal range. Twenty-year-old tw in sons had been treated with insulin since the age of 7, when both we re diagnosed with insulin-dependent diabetes mellitus (IDDM). The prob and's mother, a 68-year-old, was nondiabetic at this time. MtDNA analy sis revealed a point mutation at np 3316 in all family members, which was homoplasmic for the mutation on a photograph of agarose gel electr ophoresis containing ethidium bromide under ultraviolet light. This mu tation seemed to be maternally transmitted in the family, and the onse t of diabetes was occurring earlier and the insulin secretory capacity was declining from generation to generation, so that these findings s uggest that the point mutation at np 3316 is associated with various p henotypes of diabetes.