title: Loss of myelin-associated glycoprotein in kearns-sayre syndrome.
abstract: OBJECTIVE
  To explore myelin components and mitochondrial changes within the central nervous system in patients with well-characterized mitochondrial disorders due to nuclear DNA or mitochondrial DNA (mtDNA) mutations.
  
  
  METHODS
  Immunohistochemical analysis, histochemical analysis, mtDNA sequencing, and real-time and long-range polymerase chain reaction were used to determine the pathogenicity of mtDNA deletions.
  
  
  METHODS
  Department of Clinical Pathology, Columbia University Medical Center, and Newcastle Brain Tissue Resource.
  
  
  METHODS
  Seventeen patients with mitochondrial disorders and 7 controls were studied from August 1, 2009, to August 1, 2010.
  
  
  METHODS
  Regions of myelin-associated glycoprotein (MAG) loss.
  
  
  RESULTS
  Myelin-associated glycoprotein loss in Kearns-Sayre syndrome was associated with oligodendrocyte loss and nuclear translocation of apoptosis-inducing factor, whereas inflammation, neuronal loss, and axonal injury were minimal. In a Kearns-Sayre syndrome MAG loss region, high levels of mtDNA deletions together with cytochrome- c oxidase-deficient cells and loss of mitochondrial respiratory chain subunits (more prominent in the white than gray matter and glia than axons) confirmed the pathogenicity of mtDNA deletions.
  
  
  CONCLUSIONS
  Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination.
authors.affiliation: Mitochondrial Research Group, Institute for Aging and Health, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.
authors.forename: Nichola Z
authors.initials: NZ
authors.lastname: Lax
authors.forename: Graham R
authors.initials: GR
authors.lastname: Campbell
authors.forename: Amy K
authors.initials: AK
authors.lastname: Reeve
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ohno
authors.forename: Jessica
authors.initials: J
authors.lastname: Zambonin
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jaros
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Don J
authors.initials: DJ
authors.lastname: Mahad
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001344:Autopsy; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000209:etiology / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051792:Basic Helix-Loop-Helix Proteins; D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D013385:Succinate Dehydrogenase; D016708:Synaptophysin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C405708:OLIG2 protein, human