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.