Sequence analysis of the complete mitochondrial genome in patients with mitochondrial encephaloneuromyopathies lacking the common pathogenic DNA mutations.
The purpose of this study was to identify novel mitochondrial deoxyribonucleic acid (mtDNA) mutations in a series of patients with clinical and/or morphological features of mitochondrial dysfunction, but still no genetic diagnosis. A heterogeneous group of clinical disorders is caused by mutations in mtDNA that damage respiratory chain function of cell energy production. We developed a method to systematically screen the entire mitochondrial genome. The sequence-data were obtained with a rapid automated system. In the six mitochondrial genomes analysed we found 20 variants of the revised Cambridge reference sequence [Nat. Genet. 23 (1999) 147]. In skeletal muscle nineteen novel mtDNA variants were homoplasmic, suggesting secondary pathogenicity or co-responsibility in determination of the disease. In one patient we identified a novel heteroplasmic mtDNA mutation which presumably has a pathogenic role. This screening is therefore useful to extend the mtDNA polymorphism database and should facilitate definition of disease-related mutations in human mtDNA.
Unit of Neurology and Neurometabolic Diseases, Department of Neurological and Behavioural Sciences and Centre for Research, Therapy and Prevention of Neurohandicap, University of Siena, Italy.
Paola
P
Da Pozzo
Elena
E
Cardaioli
Elena
E
Radi
Antonio
A
Federico
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000032:analysis*; D019143:Evolution, Molecular; D005260:Female; D016678:Genome; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D004272:DNA, Mitochondrial