Loss of myelin-associated glycoprotein in kearns-sayre syndrome

Nichola Z Lax, Graham R Campbell, Amy K Reeve, Nobuhiko Ohno, Jessica Zambonin, Emma L Blakely, Robert W Taylor, Eduardo Bonilla, Kurenai Tanji, Salvatore DiMauro, Evelyn Jaros, Hans Lassmann, Doug M Turnbull, Don J Mahad

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)490-9
Number of pages10
JournalArchives of Neurology
Volume69
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords / Materials (for Non-textual outputs)

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

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