POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease

Arch Neurol. 2008 Jan;65(1):133-6. doi: 10.1001/archneurol.2007.4.


Background: Although a molecular diagnosis is possible in most patients having Charcot-Marie-Tooth disease (CMT), recessively inherited and axonal neuropathies still present a diagnostic challenge.

Objective: To determine the cause of axonal CMT type 2 in 3 siblings.

Design: Case report.

Setting: Academic research.

Participants: Three siblings who subsequently developed profound cerebellar ataxia.

Main outcome measures: Muscle biopsy specimen molecular genetic analysis of the POLG1 (polymerase gamma-1) gene, as well as screening of control subjects for POLG1 sequence variants.

Results: Cytochrome c oxidase deficient fibers and multiple deletions of mitochondrial DNA were detected in skeletal muscle. Three compound heterozygous substitutions were detected in POLG1.

Conclusion: Even in the absence of classic features of mitochondrial disease, POLG1 should be considered in patients having axonal CMT that may be associated with tremor or ataxia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Axons / pathology*
  • Charcot-Marie-Tooth Disease / diagnosis
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology*
  • Cytogenetic Analysis
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics
  • DNA-Directed DNA Polymerase / genetics*
  • Electron Transport Complex IV / genetics
  • Family
  • Female
  • Genes, Recessive / genetics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Mutation / genetics
  • Neurologic Examination
  • Pedigree
  • Peripheral Nervous System / pathology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spinocerebellar Degenerations / diagnosis
  • Spinocerebellar Degenerations / genetics
  • Spinocerebellar Degenerations / pathology


  • DNA, Mitochondrial
  • Electron Transport Complex IV
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human