title: Varying loads of the mitochondrial DNA A3243G mutation in different tissues: implications for diagnosis.
abstract: Testing for common mutations in mitochondrial DNA (mtDNA), including the A3243G MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) mutation, is routinely done in DNA isolated from blood. Since the blood level of the A3243G mutation may be low in probands and even lower in asymptomatic or oligosymptomatic maternal relatives, we assessed the proportion of A3243G mutant genomes in other accessible tissues. We studied five tissues (leukocytes, skin fibroblasts, hair roots, urinary sediment, and cheek mucosa) in 61 individuals from 22 families harboring the A3243G mutation. Although mutational loads varied widely among these tissues, as a rule DNA from urinary sediment had the highest and blood the lowest proportion of mutant genomes; individual hair roots differed markedly from one another; fibroblasts and cheek mucosa tended to have higher mutation loads than blood but lower than urinary sediment. In all individuals in whom the mutation was detectable in blood, it was also detected in other tissues. Conversely, in some individuals the mutation was undetectable in blood but clearly present in other tissues. We conclude that urinary sediment and cheek mucosa are tissues of choice for the diagnosis of mtDNA mutations, as they are easy to obtain and the mutation load is almost always greater than in blood.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Shanske
authors.forename: Jacklyn
authors.initials: J
authors.lastname: Pancrudo
authors.forename: Petra
authors.initials: P
authors.lastname: Kaufmann
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelstad
authors.forename: Sarah
authors.initials: S
authors.lastname: Jhung
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Lu
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
mesh_terms: D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics* / Q000652:urine; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006197:Hair / Q000378:metabolism; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D010375:Pedigree; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial