title: POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease.
abstract: 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.
  
  
  METHODS
  Case report.
  
  
  METHODS
  Academic research.
  
  
  METHODS
  Three siblings who subsequently developed profound cerebellar ataxia.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Essex Center for Neurological Sciences, Queen's Hospital, Romford, England.
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrower
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Stewart
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Graham
authors.initials: G
authors.lastname: Warner
authors.forename: Dominic G
authors.initials: DG
authors.lastname: O'Donovan
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Findlay
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Rajith
authors.initials: R
authors.lastname: De Silva
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001369:Axons / Q000473:pathology*; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D020732:Cytogenetic Analysis; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009460:Neurologic Examination; D010375:Pedigree; D017933:Peripheral Nervous System / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human