Varying loads of the mitochondrial DNA A3243G mutation in different tissues: Implications for diagnosis

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...

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Published in:American journal of medical genetics. Part A 2004-10, Vol.130A (2), p.134-137
Main Authors: Shanske, Sara, Pancrudo, Jacklyn, Kaufmann, Petra, Engelstad, Kristin, Jhung, Sarah, Lu, Jiesheng, Naini, Ali, DiMauro, Salvatore, De Vivo, Darryl C.
Format: Article
Language:English
Subjects:
A3243G
accessible tissues
diagnosis
DNA Mutational Analysis
DNA, Mitochondrial - blood
DNA, Mitochondrial - genetics
DNA, Mitochondrial - urine
Family Health
Female
Fibroblasts - metabolism
Hair - metabolism
Humans
Male
MELAS
MELAS Syndrome - diagnosis
MELAS Syndrome - genetics
mtDNA
Mucous Membrane - metabolism
mutation load
Pedigree
Point Mutation
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Summary: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. © 2004 Wiley‐Liss, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.30220