Distal spinal and bulbar muscular atrophy caused by dynactin mutation

Imke Puls, Shin J. Oh, Charlotte J. Sumner, Karen E. Wallace, Mary Kay Floeter, Eric A. Mann, William R. Kennedy, Gwen Wendelschafer-Crabb, Alexander Vortmeyer, Richard Powers, Kimberly Finnegan, Erika L.F. Holzbaur, Kenneth H. Fischbeck, Christy L. Ludlow

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

Impaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150 Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions.

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalAnnals of Neurology
Volume57
Issue number5
DOIs
StatePublished - May 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Puls, I., Oh, S. J., Sumner, C. J., Wallace, K. E., Floeter, M. K., Mann, E. A., Kennedy, W. R., Wendelschafer-Crabb, G., Vortmeyer, A., Powers, R., Finnegan, K., Holzbaur, E. L. F., Fischbeck, K. H., & Ludlow, C. L. (2005). Distal spinal and bulbar muscular atrophy caused by dynactin mutation. Annals of Neurology, 57(5), 687-694. https://doi.org/10.1002/ana.20468