title: Early-onset familial parkinsonism due to POLG mutations.
abstract: OBJECTIVE
  To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy.
  
  
  METHODS
  Two sisters had early-onset parkinsonism (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture, and rigidity), together with clinical and electrophysiological signs of sensorimotor axonal peripheral neuropathy.
  
  
  RESULTS
  No mutations were found in the genes for parkin or PINK1. Muscle biopsies showed ragged-red and cytochrome c oxidase-negative fibers, and biochemistry showed decreased activities of respiratory chain complexes containing mitochondrial DNA-encoded subunits. Multiple mitochondrial DNA deletions were seen by long polymerase chain reaction, and sequencing of the POLG gene showed that the patients were compound heterozygous for two patogenic mutations.
  
  
  CONCLUSIONS
  POLG mutations can cause early-onset parkinsonism in the absence of progressive external ophthalmoplegia.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Davidzon
authors.forename: Paul
authors.initials: P
authors.lastname: Greene
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Klos
authors.forename: J Eric
authors.initials: JE
authors.lastname: Ahlskog
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D004247:DNA / Q000235:genetics; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004421:Dystonia / Q000503:physiopathology; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009468:Neuromuscular Diseases / Q000503:physiopathology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D014202:Tremor / Q000503:physiopathology
chemical_list: D004272:DNA, Mitochondrial; D004247:DNA; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase