AI Article Synopsis
- A novel mutation in the DCTN1 gene has been linked to parkinsonism in a Japanese family, showing a specific change (p.Phe52Leu) not found in other similar cases.
- Affected individuals exhibit late-onset symptoms and slower disease progression, with brain imaging revealing frontotemporal atrophy, unlike the typical rapid progression seen in Perry syndrome.
- This research highlights the potential role of DCTN1 mutations in various neurodegenerative diseases and suggests that understanding dynactin's role in cargo transport could provide further insights.
Article 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.
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| http://dx.doi.org/10.1002/mds.25833 | DOI Listing |
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