Loss of myelin-associated glycoprotein in kearns-sayre syndrome

Arch Neurol. 2012 Apr;69(4):490-9. doi: 10.1001/archneurol.2011.2167.


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.

Design: Immunohistochemical analysis, histochemical analysis, mtDNA sequencing, and real-time and long-range polymerase chain reaction were used to determine the pathogenicity of mtDNA deletions.

Setting: Department of Clinical Pathology, Columbia University Medical Center, and Newcastle Brain Tissue Resource.

Patients: Seventeen patients with mitochondrial disorders and 7 controls were studied from August 1, 2009, to August 1, 2010.

Main outcome measure: 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.

Conclusion: Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Autopsy
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Case-Control Studies
  • DNA Mutational Analysis
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / metabolism
  • Female
  • Gene Deletion
  • Gene Expression Regulation / genetics
  • Humans
  • Kearns-Sayre Syndrome / complications
  • Kearns-Sayre Syndrome / genetics
  • Kearns-Sayre Syndrome / metabolism*
  • Kearns-Sayre Syndrome / pathology*
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / metabolism*
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / metabolism*
  • Nerve Degeneration / etiology
  • Nerve Degeneration / genetics
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Retrospective Studies
  • Succinate Dehydrogenase / metabolism
  • Synaptophysin / metabolism
  • Young Adult


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Basic Helix-Loop-Helix Transcription Factors
  • CD68 antigen, human
  • DNA, Mitochondrial
  • Myelin Basic Protein
  • Myelin-Associated Glycoprotein
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Synaptophysin
  • Succinate Dehydrogenase
  • Electron Transport Complex IV