POINT MUTATION OF THE MITOCHONDRIAL TRNA(LEU) GENE (A-3243-G) IN MATERNALLY INHERITED HYPERTROPHIC CARDIOMYOPATHY, DIABETES-MELLITUS, RENAL-FAILURE, AND SENSORINEURAL DEAFNESS

The A 3243 G mutation of the mitochondrial tRNA(Leu) gene was found to segregate with maternally inherited diabetes mellitus, sensorineural deafness, hypertrophic cardiomyopathy, or renal failure in a large ped igree of 35 affected members in four generations. Presenting symptoms almost consistently involved deafness and recurrent attacks of migrain e-like headaches, but the clinical course of the disease varied within and across generations. The A 3243 G mutation has been previously rep orted in association with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome (MELAS) and with diabetes m ellitus and deafness. To our knowledge, however, hypertrophic cardiomy opathy is not a common feature in people with the A 3243 G mutation an d renal failure has not been hitherto reported in association with thi s mutation. The present observation gives additional support to the va riable clinical expression of mtDNA mutations in humans.