Abstract
A 29-year-old man presented with rapidly progressive severe neck weakness, asymmetrical bilateral upper extremity weakness, bulbar dysfunction, profound muscle wasting, and weight loss. Within 1 year, his speech became unintelligible, he became gastrostomy- and tracheostomy/ventilator-dependent, and wheelchair bound. Electrophysiology suggested motor neuron disease. Whole exome sequencing revealed a heterozygous pathogenic variant in the fused in sarcoma gene (FUS), c.1574C>T,p. R525L, consistent with autosomal dominant amyotrophic lateral sclerosis. Autopsy revealed extensive denervation atrophy of skeletal musculature. Surprisingly, there was only minimal patchy depletion of motor neurons within the cervico-thoracic spinal cord anterior horn cells, and the tracts were largely preserved. TDP-43 inclusions were absent. Abnormal expression of FUS mutation product (cytoplasmic inclusions) was demonstrated by immunohistochemistry within anterior horn motor neurons. The most prominent finding was a disparity between profound neck weakness and relatively low-grade anterior horn cell loss or tract degeneration in the cervico-thoracic cord.
Original language | English (US) |
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Pages (from-to) | 365-369 |
Number of pages | 5 |
Journal | Journal of neuropathology and experimental neurology |
Volume | 79 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2020 |
Externally published | Yes |
Keywords
- Amyotrophic lateral sclerosis (ALS)
- Cytoplasmic inclusions
- Fused in sarcoma gene (FUS)
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience