In a 24-year-old man with sporadic ALS (105400), Alexander et al. (2002) identified a heterozygous 112A-G transition in exon 4 of the SOD1 gene, resulting in a his80-to-arg (H80R) substitution. The patient presented with a 4-month history of left leg weakness, and developed rapidly progressive weakness in all 4 limbs and bulbar musculature, manifesting as quadriplegia, dysarthria, and dysphagia over the subsequent 8 months. He died from pneumonia 18 months after the onset of symptoms. Neuropathologic examination showed anterior horn cell degeneration, prominent gliosis, and Bunina bodies in both the spinal cord and brain stem. There was no involvement of the corticospinal tract. Ubiquitinated inclusions were demonstrated within anterior horn cells, and SOD1-immunoreactive inclusions were identified. There was no family history of any form of neuromuscular disorder. His parents, maternal grandfather, and 2 sibs did not carry the mutation, and it was not identified in 150 unaffected Irish controls. (Alexander et al. (2002) reported the mutation as histidine to arginine at codon 80, but incorrectly symbolized the mutation as H80A.)
