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.
References
Oct 11, 2005·Okajimas Folia Anatomica Japonica·Jun SuzukiTadashi Hisamitsu
Oct 14, 2009·Nature Reviews. Genetics·Patrick A DionGuy A Rouleau
Jul 30, 2010·Neurology·D BäumerO Ansorge
May 24, 2011·Acta Neuropathologica·Ian R A MackenzieManuela Neumann
Sep 17, 2011·Journal of Neurology, Neurosurgery, and Psychiatry·Chieko Fujimura-KiyonoToshiaki Hanafusa
May 1, 2012·Journal of Neurology, Neurosurgery, and Psychiatry·Tadashi KanouchiTakanori Yokota
Dec 27, 2013·Nature Neuroscience·Alan E RentonBryan J Traynor
Jun 3, 2015·Disease Models & Mechanisms·Jessica LenziIrene Bozzoni
Oct 11, 2015·Acta Neuropathologica Communications·Andrew KingSafa Al-Sarraj
Oct 31, 2015·Neurologic Clinics·Shahram SaberiJohn Ravits
Feb 5, 2016·Nature Communications·Aarti SharmaNeil A Shneider
Apr 2, 2016·Brain Research·Yulei Shang, Eric J Huang
Mar 1, 2017·Acta Neuropathologica·Jelena Scekic-ZahirovicLuc Dupuis
Aug 16, 2017·Neurology. Genetics·Lisha KuangHaining Zhu
Nov 7, 2017·Nature Medicine·Clemens DuerrschmidAtul R Chopra
Jan 31, 2018·Glia·Azadeh KiaPiera Pasinelli
Jul 3, 2018·Seminars in Pediatric Neurology·Ian R WoodcockEppie M Yiu