Abstract | BACKGROUND: AIMS: To present an audit of the MNRI mtDNA diagnostic service between 1990 and 2001, encompassing 1725 referred patients. METHODS: The detection techniques carried out included polymerase chain reaction amplification of mtDNA combined with restriction fragment length polymorphism analysis for mtDNA point mutation detection, supplemented with selected sequence analysis and Southern blots for the detection of deletions/ rearrangements. Tissues tested included blood, hair and skeletal muscle. RESULTS: Of the 1184 patients screened for MELAS A3243G, 6.17% were positive for the mutation, whereas for MERRF A8344G, 2.21% carried the mutation and for LS/NARP T8993C/G, 0.32% carried the mutation. The outcomes for the LHON mutations were G11778A, 6.60%, T14484C, 5.76% and G3460A, 0.29%. Of the patients referred for KSS and CPEO, 17.72% had deletions/rearrangements. CONCLUSIONS: Overall, the detection rate of mtDNA point mutations was low. The protean clinical features of mitochondrial disorders and the frequency of partial phenotypes lead to requests for tests in many patients with a relatively low likelihood of mtDNA mutations. An improved algorithm could involve mutation screening appropriate to the phenotype using sequencing of selected mtDNA regions in patients with a high likelihood of mtDNA disease. Features increasing the likelihood of mtDNA mutations include the following: (i) a typical phenotype, (ii) a maternal inheritance pattern and (iii) histochemical evidence of mitochondrial abnormality in the muscle biopsy. Efficient laboratory diagnosis of mtDNA disease involves good communication between the physician and laboratory scientists, coupled with screening of the appropriate tissue.
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Authors | R Marotta, J Chin, A Quigley, S Katsabanis, R Kapsa, E Byrne, S Collins |
Journal | Internal medicine journal
(Intern Med J)
2004 Jan-Feb
Vol. 34
Issue 1-2
Pg. 10-9
ISSN: 1444-0903 [Print] Australia |
PMID | 14748908
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Adult
- Australia
- Blotting, Southern
- DNA, Mitochondrial
(genetics)
- Humans
- Mitochondrial Diseases
(diagnosis)
- Mutation
- Point Mutation
- Polymerase Chain Reaction
- Polymorphism, Restriction Fragment Length
- Sequence Analysis, DNA
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