Heterogeneous presentation in A3243G mutation in the mitochondrial tRNALeu(UUR) gene

Abstract

Conclusion-The most severe clinical phenotype, LS 3243, was associated with the highest proportion of the A3243G mutation as well as the most prominent histological and biochemical abnormalities. (Arch Dis Child 2000;82:407-411)

An Autopsy Case of Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes Syndrome with Chronic Renal Failure.

“…While renal tubular dysfunction is generally associated with a large deletion in mtDNAor rarely with duplication (2-7, 13-15), all the reported cases involving glomerular lesions were associated with the adenine to guanine transition at position 3243 of the mitochondrial tRNAleu gene (7-ll, 13, 17-19). The 3243 mutation was originally detected in MELASsyndrome (20), and recently the same mutation has been found in some patients with non-MELAS-associated phenotypes including PEO (progressive external ophthalmoplegia), maternally inherited diabetes mellitus, sensorineunal hearing loss, hypertrophic cardiomyopathy, and hereditary glomerulopathy (21)(22)(23)(24)(25)(26)(27). Some types of glomerulonephritis, such as focal segmental glomerulosclerosis, should be seen as a phenotypic expression of this mutation.…”

Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan

“…Though the protein subunits of the mitochondrial respiratory chain enzymes are predominantly encoded by nuclear genes, some mitochondrial DNA (mtDNA) mutations are pathogenic in LS, mainly T fi G or T fi C point mutations occurring at nucleotide position (np) 8993 (8993 mutation) (Tatuch et al 1992;Santorelli et al 1993;de Vries et al 1993) and T fi C or T fi G at np9176 (Thyagarajan et al 1995;Campos et al 1997;Makino et al 1998). Rare mtDNA mutations such as A3243G, A8344G, and C11777A have also been reported (Koga et al 2000;Berkovic et al 1991;Komaki et al 2003).…”

Comparison of mitochondrial A3243G mutation loads in easily accessible samples from a family with maternally inherited diabetes and deafness

“…Although the heteroplasmic percentages of mutant mitochondrial DNA vary among tissues, it is difficult to speculate on the heteroplasmic percentages of mutant mitochondrial DNA in a specific organ (such as skeletal muscle, the brain and the pancreatic islet). Results from leukocyte samples can supply information on the heteroplasmic mutation loads in leukocytes, which is clinically useful to some extent (4,6,7). However, the usefulness of DNA from other easily accessible samples (hair roots, buccal scraping and urinary sediment) has been insufficiently evaluated.…”

“…This same mutation can cause other clinical manifestations of mitochondrial multisystem disorders, such as maternally inherited diabetes and deafness (MIDD), myoclonus epilepsy with ragged red fibers, progressive external ophthalmoplegia, hypertrophic cardiomyopathy and the Leigh syndrome (2). The A3243G mutation load in different organs and tissues in association with heteroplasmy may explain which clinical presentations occur among patients who carry the mutation (2)(3)(4)(5). Usually, DNA from blood leukocytes or muscle biopsy samples is subjected to mitochondrial mutation analysis.…”