Source:http://linkedlifedata.com/resource/pubmed/id/11063732
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0010760,
umls-concept:C0012929,
umls-concept:C0017337,
umls-concept:C0030705,
umls-concept:C0039082,
umls-concept:C0079380,
umls-concept:C0181586,
umls-concept:C0205314,
umls-concept:C0221099,
umls-concept:C0392760,
umls-concept:C0679622,
umls-concept:C1537987,
umls-concept:C1706853,
umls-concept:C1879748
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| pubmed:issue |
18
|
| pubmed:dateCreated |
2000-11-28
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| pubmed:abstractText |
We report on a novel frameshift mutation in the mtDNA gene encoding cytochrome c oxidase (COX) subunit III. The proband is an 11-year-old girl with a negative family history and an apparently healthy younger brother. Since 4 years of age, she has developed a progressive spastic paraparesis associated with ophthalmoparesis and moderate mental retardation. The presence of severe lactic acidosis and Leigh-like lesions of putamina prompted us to perform muscle and skin biopsies. In both, a profound, isolated defect of COX was found by histochemical and biochemical assays. Sequence analysis of muscle mtDNA resulted in the identification of a virtually homoplasmic frameshift mutation in the COIII gene, due to the insertion of an extra C at nucleotide position 9537 of mtDNA. Although the 9537C(ins) does not impair transcription of COIII, no full-length COX III protein was detected in mtDNA translation assays in vivo. Western blot analysis of two-dimensional blue-native electrophoresis showed a reduction of specific crossreacting material and the accumulation of early-assembly intermediates of COX, whereas the fully assembled complex was absent. One of these intermediates had an electrophoretic mobility different from those seen in controls, suggesting the presence of a qualitative abnormality of COX assembly. Immunostaining with specific antibodies failed to detect the presence of several smaller subunits in the complex lacking COX III, in spite of the demonstration that these subunits were present in the crude mitochondrial fraction of patient's cultured fibroblasts. Taken together, the data indicate a role for COX III in the incorporation and maintenance of smaller COX subunits within the complex.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
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| pubmed:issn |
0964-6906
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
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| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2733-42
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:11063732-Base Sequence,
pubmed-meshheading:11063732-Blotting, Northern,
pubmed-meshheading:11063732-Blotting, Western,
pubmed-meshheading:11063732-Child,
pubmed-meshheading:11063732-Child, Preschool,
pubmed-meshheading:11063732-DNA, Mitochondrial,
pubmed-meshheading:11063732-Electron Transport Complex IV,
pubmed-meshheading:11063732-Female,
pubmed-meshheading:11063732-Fibroblasts,
pubmed-meshheading:11063732-Frameshift Mutation,
pubmed-meshheading:11063732-Genetic Complementation Test,
pubmed-meshheading:11063732-Humans,
pubmed-meshheading:11063732-Hybrid Cells,
pubmed-meshheading:11063732-Intellectual Disability,
pubmed-meshheading:11063732-Leigh Disease,
pubmed-meshheading:11063732-Magnetic Resonance Spectroscopy,
pubmed-meshheading:11063732-Male,
pubmed-meshheading:11063732-Mutagenesis, Insertional,
pubmed-meshheading:11063732-Paraparesis, Spastic,
pubmed-meshheading:11063732-Pedigree,
pubmed-meshheading:11063732-Polymorphism, Restriction Fragment Length,
pubmed-meshheading:11063732-Protein Biosynthesis,
pubmed-meshheading:11063732-RNA, Messenger
|
| pubmed:year |
2000
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| pubmed:articleTitle |
A novel frameshift mutation of the mtDNA COIII gene leads to impaired assembly of cytochrome c oxidase in a patient affected by Leigh-like syndrome.
|
| pubmed:affiliation |
Istituto Nazionale Neurologico C. Besta, Via Celoria 11, 20133 Milano, Italy.
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| pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't
|