• Eiichi Araki, Yoshio Tsuboi, Justus Daechsel, Austen Milnerwood, Carles Vilarino-Guell, Naoki Fujii, Takayasu Mishima, Takayuki Oka, Hideo Hara, Jiro Fukae, and Matthew J Farrer.
• Department of Neurology, National Omuta Hospital, Fukuoka, Japan.
• Mov. Disord. 2014 Aug 1; 29 (9): 1201-4.

BackgroundDepression, parkinsonism, and hypoventilation (Perry syndrome) or familial motor neuron disease have been linked to mutations in dynactin P150(Glued) (DCTN1).MethodsWe 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.ResultsA 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) .ConclusionsDCTN1 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.© 2014 International Parkinson and Movement Disorder Society.

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