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Am J Hum Genet. Mar 1991; 48(3): 492–501.
PMCID: PMC1682992

mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.


We studied two related infants with a fatal mitochondrial disease, affecting muscle in one and liver in the other. Quantitative analysis revealed a severe depletion of mtDNA in affected tissues. This genetic abnormality was also observed in muscle of an unrelated infant with myopathy and in muscle and kidney of a fourth child with myopathy and nephropathy. Biochemistry, immunohistochemistry, and in situ hybridization showed that the depletion of mtDNA in muscle fibers was correlated with a respiratory chain defect and with lack of mitochondrially translated proteins. Although the differential tissue involvement in these infants suggests mtDNA heteroplasmy, sequence analysis of mtDNA replication origins did not reveal any abnormality that could account for the low copy number.

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