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Mov Disord. 2014 Aug;29(9):1201-4. doi: 10.1002/mds.25833. Epub 2014 Feb 22.

A novel DCTN1 mutation with late-onset parkinsonism and frontotemporal atrophy.

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1
Department of Neurology, National Omuta Hospital, Fukuoka, Japan.

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.

KEYWORDS:

Parkinson's disease; Perry syndrome; genetics; parkinsonism

PMID:
24676999
DOI:
10.1002/mds.25833
[Indexed for MEDLINE]
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