Human Mitochondrial Leucyl-tRNA Synthetase Corrects Mitochondrial Dysfunctions Due to the tRNA A3243G Mutation, Associated with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms and Diabetes Ronghua Li and Min-Xin Guan* Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, and Department of Pediatrics, University of Cincinnati Coll...

BACKGROUND Focal segmental glomerulosclerosis (FSGS) is a major cause of steroid-resistant nephrotic syndrome in childhood with a central role for the podocytes in the pathogenesis. Mutated proteins expressed in podocytes cause proteinuria. The role of combined gene defects in the development of FSGS is less clear. METHODS We analysed seven podocyte genes known to cause proteinuria and FSGS i...

The majority of pathogenic mitochondrial DNA (mtDNA) mutations are heteroplasmic, with both mutant and wild-type alleles present within the same individual. MtDNA is transmitted only from females to their offspring but a single female can bear offspring who harbour different levels of mutant mtDNA and have a variable phenotype. In single families, this complex genetic and phenotypic variability...

Pancreatic beta-cells are able to respond to nutrients, principally glucose, as the primary stimulus for insulin exocytosis. This unique feature requires translation of metabolic substrates into intracellular messengers recognized by the exocytotic machinery. Central to this signal transduction mechanism, mitochondria integrate and generate metabolic signals, thereby coupling glucose recognitio...

A 6 year old Portuguese boy with dilated cardiomyopathy had abundant ragged red fibres in muscle (20% of total) and severe lactic acidosis. Molecular genetic analysis showed the A to G transition in the mitochondrial transfer RNALeu(UUR) gene at nt 3243 ("MELAS mutation"), which accounted for 88% and 68% of the total mtDNA in his muscle and blood, respectively. Molecular studies in blood from 1...

PURPOSE It has been suggested that mitochondrial disease may be responsible for a substantial proportion of strokes of indetermined origin. We have preliminarily screened for MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) mutations in young patients with cryptogenic strokes. METHOD The mitochondrial mutations A3243G and T3271C were investigated in 38 subjec...

AIM We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. MATERIAL AND METHODS DNA sequencing was used to detect and val...