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PMID: 1998336 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

American journal of human genetics ·Vol. 48 ·No. 3 ·1991-03-00 ·Pages 492-501

Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E, Schon EA, DiMauro S

Abstract

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.

MeSH Terms
Blotting, Southern Brain Diseases/genetics Chromosome Aberrations DNA, Mitochondrial/chemistry Female Gene Amplification Gene Expression Humans Infant, Newborn Male Mitochondria/pathology Mitochondria, Liver/chemistry,ultrastructure Mitochondria, Muscle/chemistry,ultrastructure Pedigree
Chemicals
DNA, Mitochondrial
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Moraes C T
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY.
Shanske S
Tritschler H J
Aprille J R
Andreetta F
Bonilla E
Schon E A
DiMauro S
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1991-03-00
Pages
492-501
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1682992
Subset
IM
Grants
NINDS NIH HHS · NS 11766 · United States
External Links
PubMed source PMC Full Text View journal details
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