Mutations in the mitochondrial tRNA(Leu(UUR)) gene are associated with a large variety of human diseases through a largely undisclosed mechanism. The A3243G tRNA(Leu(UUR)) mutation leads to reduction of mitochondrial DNA (mtDNA)-encoded proteins and oxidative phosphorylation activity even when the cells are competent in mitochondrial translation. These two aspects led to the suggestion that a d...

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...

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...

BACKGROUND the maternally inherited MTTL1 A3243G mutation in the mitochondrial genome causes MelaS (Mitochondrial encephalopathy lactic acidosis with Stroke-like episodes), a condition that is multisystemic but affects primarily the nervous system. Significant intra-familial variation in phenotype and severity of disease is well recognized. METHODS retrospective and ongoing study of an extend...

We report on a case of a 48-year-old woman presenting with maternally inherited diabetes mellitus and deafness (MIDD) syndrome. Molecular genetic analysis and clinical evaluation were conducted in the patient and her 4 children to investigate the interrelation between an MIDD-associated mitochondrial DNA (mtDNA) mutation and clinical manifestations. Various symptoms and markers of MIDD, includi...

INTRODUCTION The mitochondrial DNA A3243G point mutation is associated with a wide variety of systemic manifestations including a macular dystrophy. The characteristics of fundus autofluorescence (AF) in these patients are distinctive and have not been previously described. METHODS A complete history and ophthalmic examination, including fundus photography and autofluorescence imaging, was pe...

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...