Single-fiber analysis of mitochondrial A3243G mutation in four different phenotypes

• Published in: Acta neuropathologica Vol. 99; no. 2; pp. 186 - 190
• Main Authors: KOGA, Y, KOGA, A, IWANAGA, R, AKITA, Y, TUBONE, J, MATSUISHI, T, TAKANE, N, SATO, Y, KATO, H
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.2000; Springer Nature B.V
• Subjects: Acidosis; Adenine; Adult; Biological and medical sciences; Child; Diabetes mellitus; Diabetes Mellitus - genetics; Diabetes Mellitus - pathology; Diseases of striated muscles. Neuromuscular diseases; DNA, Mitochondrial - genetics; Encephalopathy; Guanine; Humans; Lactic acidosis; Leigh Disease - genetics; Leigh Disease - pathology; Medical sciences; MELAS syndrome; MELAS Syndrome - genetics; MELAS Syndrome - pathology; Middle Aged; Mitochondrial DNA; Muscle Fibers, Skeletal - pathology; Muscle, Skeletal - pathology; Mutation; Myopathy; Neurology; Ophthalmoplegia; Ophthalmoplegia, Chronic Progressive External - genetics; Ophthalmoplegia, Chronic Progressive External - pathology; Patients; Phenotypes; Point Mutation; Stroke-like episodes; Endocrinopathy; Leigh disease; Mitochondrial DNA; Enzymopathy; Mitochondrial disorder; Oculomotor syndrome; Human; Nervous system diseases; Diabetes mellitus; Metabolic diseases; Exploration; Congenital disease; Cerebral disorder; Genetic disease; Progressive; Polymerase chain reaction; Eye disease; Striated muscle disease; Central nervous system disease; External; Ophthalmoplegia; Mitochondrial myopathy; Lactic acid; Mutation; Acidosis; Molecular biology; MELAS syndrome
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/pl00007423

Five unrelated patients harboring the A3243G mutation in the mitochondrial DNA (mtDNA) but presenting with different clinical phenotype were studied for their percentage of mutation at the single muscle fiber levels. One patient had a clinically and pathologically defined Leigh syndrome (LS), two showed mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), another showed progressive external ophthalmoplegia (PEO), and the other showed mitochondrial diabetes mellitus (MDM). The mutation load was greater in the muscle from the patient with LS (92%), who showed more than 80% even in the non-ragged red fibers (RRF) and also presented the highest proportion of RRF. The patients with MELAS had lower mutation levels as well as a lower proportion of RRF, and these two parameters were even lower in the PEO and MDM patients. These results were consistent with the concept that differences in the mutation load and in the somatic distribution of the mutation among different cells and tissues are responsible for the differences in phenotypical expression of the disease.