The mitochondrial A3243G mutation is most commonly related to the MELAS syndrome, but can cause many different clinical manifestations at various ages. Here, we present a family with maternally inherited diabetes and deafness (MIDD), the proband of which exhibits hearing loss, diabetes mellitus, cardiomyopathy and short stature. Four easily accessible samples (whole blood, hair roots, buccal sc...

AIMS To report on a family with five members who carry the A3243G mutation in mitochondrial tRNA for leucine 1 (MTTL1) and present with diabetes, chronic intestinal pseudo-obstruction (CIPO) and recurrent pancreatitis, and to screen for this mutation in a cohort of 36 unrelated patients with recurrent pancreatitis. METHODS The mutation was quantified in several tissue samples from patients. R...

The A3243G mutation in the mitochondrial gene for human mitochondrial (mt) tRNA(Leu(UUR)), responsible for decoding of UUR codons, is associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We previously demonstrated that this mutation causes defects in 5-taurinomethyluridine (taum(5)U) modification at the anticodon first (wobble) position of th...

OBJECTIVE To determine whether there are common symptoms within different phenotypes of the mitochondrial DNA A3243G mutation. DESIGN A series of 52 adults with mitochondrial encephalomyopathies and their symptomatic relatives were screened for the A3243G mutation using restriction enzyme analysis. In addition to clinical examination, patients with the mutation underwent audiometry. RESULTS...

Segregation of mitochondrial DNA (mtDNA) is an important underlying pathogenic factor in mtDNA mutation accumulation in mitochondrial diseases and aging, but the molecular mechanisms of mtDNA segregation are elusive. Lack of high-throughput single-cell mutation load assays lies at the root of the paucity of studies in which, at the single-cell level, mitotic mtDNA segregation patterns have been...

Mutant mitochondrial (mt) DNA variants are related to human disease and have been investigated using cytoplasmic hybrid (cybrid) cells generated from human tumor cells in which mutant mt maintenance depends on the cell line. It is, however, unclear whether human intercellular fusion of non-tumorous cells influences the maintenance of disease-related mutant mt. A preliminary experiment of cell-c...

The A3243G mutation within the human mitochondrial (hs mt) tRNALeuUUR gene is associated with maternally inherited deafness and diabetes (MIDD) and other mitochondrial encephalopathies. One of the most pronounced structural effects of this mutation is the disruption of the native structure through stabilization of a high-affinity dimeric complex. We conducted a series of studies that address th...

BACKGROUND Mitochondrial DNA point mutations are especially deleterious to tissues with high energy demand, including the peripheral nervous system. Neuropathy has been associated with several mitochondrial diseases, including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). OBJECTIVE To evaluate nerve conduction in a genotypically and phenotypically homogene...