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Distal spinal and bulbar muscular atrophy caused by dynactin mutation
Author(s) -
Puls Imke,
Oh Shin J.,
Sumner Charlotte J.,
Wallace Karen E.,
Floeter Mary Kay,
Mann Eric A.,
Kennedy William R.,
WendelschaferCrabb Gwen,
Vortmeyer Alexander,
Powers Richard,
Finnegan Kimberly,
Holzbaur Erika L. F.,
Fischbeck Kenneth H.,
Ludlow Christy L.
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20468
Subject(s) - motor neuron , dynactin , amyotrophic lateral sclerosis , spinal muscular atrophy , neuroscience , dynein , neurofilament , axoplasmic transport , pathology , anatomy , atrophy , anterior horn cell , biology , spinal cord , medicine , microtubule , immunohistochemistry , disease , microbiology and biotechnology
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. Ann Neurol 2005;57:687–694