Mutations in mitochondrial tRNA genes are associated with a wide spectrum of human diseases. In particular, the tRNA(Leu(UUR)) A3243G mutation causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms (MELAS) and 2% of cases of type 2 diabetes. The primary defect in this mutation was an inefficient aminoacylation of the tRNA(Leu(UUR)). In the present study, we have inves...

We report on pancreatic exocrine dysfunction in families that have the mitochondrial tRNA(Leu)(UUR) gene mutation. These families exhibited maternally inherited diabetes mellitus (DM) and an A to G substitution at nt 3243 of the mitochondrial tRNA(Leu)(UUR) gene (A3243G mutation). Pancreatic necropsy samples from one proband showed accumulation of degenerated mitochondria in pancreatic acinar c...

Diabetes mellitus (DM) is a polygenic complex disorder, characterized by a disturbance in insulin production by the pancreatic beta-cell or in the ability of target tissues to respond to insulin. The adult onset non-insulin dependent or type 2 DM, in particular, clearly demonstrates the interplay between genetic and nutritional factors in the pathomechanism of this disorder. The importance of t...

The mitochondrial DNA mutation MTTL1 A3243G causes MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes). The A3243G mutation is also associated with variable endocrinopathies. We describe 2 case histories of patients with the A3243G mutation. The first patient presented with diabetes and uncontrolled Graves’ thyrotoxicosis in association with a strokelike epis...

Mitochondrial diabetes is characterized by diabetes and hearing loss in maternal transmission with a heteroplasmic A3243G mutation in the mitochondrial gene. In patients with the mutation, it has been reported that hepatic involvement is rarely observed. We demonstrated a case of hypertrophic cardiomyopathy and hepatic failure with mitochondrial diabetes. To clarify the pathogenesis we analyzed...

The mitochondrial DNA A3243G mutation causes neuromuscular disease. To investigate the muscle-specific pathophysiology of mitochondrial disease, rhabdomyosarcoma transmitochondrial hybrid cells (cybrids) were generated that retain the capacity to differentiate to myotubes. In some cases, striated muscle-like fibres were formed after innervation with rat embryonic spinal cord. Myotubes carrying ...

The genotype-phenotype relationship in diseases with mtDNA point mutations is still elusive. The maintenance of wild-type mtDNA copy number is essential to the normal mitochondrial oxidative function. This study examined the relationship between mtDNA copy number in blood and urine and disease severity of the patients harboring A3243G mutation. We recruited 115 A3243G patients, in which 28 were...

BACKGROUND The A3243G mitochondrial tRNA leu(UUR) point mutation causes mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, the most common mitochondrial DNA (mtDNA) disorder, and is also found in patients with maternally inherited diabetes and deafness syndrome (MIDD). To correlate disease manifestation with mutation loads, it is necessary to mea...

Background:. A3243G mutation in tRNA Leu (UUR) leads to a specific clinical syndrome characterized by diabetes and sensorineural hearing defect, hence called as “Maternally Inherited Diabetes and Deafness (MIDD)”.. Methods: The study was retrospective, analytical case control study. Non probability convenient sampling technique was used. Subjects were divided into two groups. Thirty-nine patien...

OBJECTIVES/HYPOTHESIS To evaluate vestibular function in patients with the mitochondrial A3243G mutation. STUDY DESIGN Data from patients with the A3243G mutation attending an academic tertiary referral center were prospectively recorded. METHODS The clinical histories of 13 unrelated patients with the mitochondrial A3243G mutation (six mitochondrial encephalomyopathy, lactic acidosis, and ...