title: A novel DCTN1 mutation with late-onset parkinsonism and frontotemporal atrophy.
abstract: BACKGROUND
  Depression, parkinsonism, and hypoventilation (Perry syndrome) or familial motor neuron disease have been linked to mutations in dynactin P150(Glued) (DCTN1).
  
  
  METHODS
  We employed genealogic, clinical, neurologic, and MRI investigations, as well as analysis of genes implicated in parkinsonism. Cellular transfection, immunocytochemistry, and immunoprecipitation analysis of wild-type (WT) and mutant DCTN1 were also performed.
  
  
  RESULTS
  A novel heterozygous mutation, DCTN1 c.156T>G, encoding p.Phe52Leu, segregates with parkinsonism in a Japanese family. The substitution was not observed in affected probands with familial parkinsonism or control subjects and is evolutionarily conserved. In contrast to Perry syndrome, affected carriers have late-onset disease and slower progression, with frontotemporal atrophy revealed by MRI. In vitro studies suggest the mutant protein has impaired microtubule binding, compared to WT dynactin p150(Glued) .
  
  
  CONCLUSIONS
  DCTN1 mutations may contribute to disparate neurodegenerative diagnoses, including familial motor neuron disease, parkinsonism, and frontotemporal atrophy, and further studies of dynactin-mediated cargo transport may prove insightful.
authors.affiliation: Department of Neurology, National Omuta Hospital, Fukuoka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Justus
authors.initials: J
authors.lastname: Daechsel
authors.forename: Austen
authors.initials: A
authors.lastname: Milnerwood
authors.forename: Carles
authors.initials: C
authors.lastname: Vilarino-Guell
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujii
authors.forename: Takayasu
authors.initials: T
authors.lastname: Mishima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Oka
authors.forename: Hideo
authors.initials: H
authors.lastname: Hara
authors.forename: Jiro
authors.initials: J
authors.lastname: Fukae
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D017668:Age of Onset; D000368:Aged; D001284:Atrophy; D016207:Cytokines / Q000378:metabolism; D000072159:Dynactin Complex; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D005820:Genetic Testing; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008870:Microtubules / Q000473:pathology; D008875:Middle Aged; D009460:Neurologic Examination; D020734:Parkinsonian Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014162:Transfection
chemical_list: D016207:Cytokines; C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins
keywords: Parkinson's disease; Perry syndrome; genetics; parkinsonism