title: Reversible infantile respiratory chain deficiency: a clinical and molecular study.
abstract: OBJECTIVE
  To characterize the clinical features and clarify the pathogenicity of "benign cytochrome c oxidase deficiency myopathy."
  
  
  METHODS
  The study included 8 patients with the phenotype of this disease. Six patients underwent muscle biopsies and all the 8 underwent mitochondrial DNA analyses. To confirm the pathogenicity of the detected mitochondrial DNA mutation, we performed northern blot analysis, using muscle specimens, and blue native polyacrylamide gel electrophoresis and respiratory chain enzyme activity assay of transmitochondrial cell lines (cybrids).
  
  
  RESULTS
  Clinical symptoms were limited to skeletal muscle and improved spontaneously in all cases; however, 2 siblings had basal ganglia lesions. In all patients, we identified a homoplasmic m.14674T>C or m.14674T>G mitochondrial transfer RNA-glutamate mutation. Northern blot analysis revealed decreased levels of mitochondrial transfer RNA-glutamate molecules. Muscle specimens and cybrids derived from patients showed decreased activity of respiratory complexes IV, and/or I, III; however, this was normal in naive myoblasts.
  
  
  CONCLUSIONS
  Identification of a novel m.14674T>G mutation in addition to m.14674T>C indicated the importance of this site for disease causation. Analyses of cybrids revealed the pathogenicity of m.14674T>C mutation, which resulted in defects of cytochrome c oxidase and multiple respiratory chain enzymes. Furthermore, patients with basal ganglia lesions provided new insights into this disease, in which only skeletal muscle was thought to be affected. Normal respiratory chain enzyme activities in naive myoblasts suggested the compensatory influence of nuclear factors, which may be a clue to understanding the mechanisms of spontaneous recovery and low penetrance in families carrying the mutation.
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Mimaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hatakeyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Komaki
authors.forename: Mina
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Hidee
authors.initials: H
authors.lastname: Arai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kirino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000473:pathology; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D018698:Glutamic Acid; D012343:RNA, Transfer; D003576:Electron Transport Complex IV