title: Mitochondrial myopathies: clinical and biochemical features of 30 patients with major deletions of muscle mitochondrial DNA.
abstract: Analysis of mitochondrial DNA (mtDNA) in muscle and blood from 72 patients with mitochondrial myopathy showed that 30 had major deletions of a variable proportion of muscle mtDNA. All of these 30 patients presented with progressive external ophthalmoplegia and limb weakness, and 8 had the additional features of the Kearns-Sayre syndrome. Of the 42 patients without detectable muscle mtDNA deletions, 10 had progressive external ophthalmoplegia and limb weakness, 2 had the Kearns-Sayre syndrome, 11 had limb weakness without extraocular involvement, and 19 had multisystem disorders predominantly affecting the central nervous system. Only 2 patients with mtDNA deletions had clinically affected relatives, compared with 10 of those without deletions. In the 4 patients with polarographic defects exclusively involving complex I (NADH coenzyme Q reductase), the deleted protein-coding genes were confined to those for complex I subunits. Thirteen other patients with apparently identical deletions had variable clinical and biochemical features. Immunoblots of complex I polypeptides from patients with deletions were either indistinguishable from controls or showed only a mild generalized decrease in all identifiable subunits.
authors.affiliation: University Department of Clinical Neurology, Institute of Neurology, Queen Square, London, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Holt
authors.forename: A E
authors.initials: AE
authors.lastname: Harding
authors.forename: J M
authors.initials: JM
authors.lastname: Cooper
authors.forename: A H
authors.initials: AH
authors.lastname: Schapira
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: J B
authors.initials: JB
authors.lastname: Clark
authors.forename: J A
authors.initials: JA
authors.lastname: Morgan-Hughes
mesh_terms: D000328:Adult; D002872:Chromosome Deletion; D003580:Cytochromes / Q000235:genetics; D004272:DNA, Mitochondrial / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology*; D009135:Muscular Diseases / Q000235:genetics*
chemical_list: D003580:Cytochromes; D004272:DNA, Mitochondrial