Familial amyotrophic lateral sclerosis with bulbar onset and a novel Asp101Tyr Cu/Zn superoxide dismutase gene mutation.

We describe a patient with familial amyotrophic lateral sclerosis (FALS) in whom we identified a novel missense mutation in exon 4 (Asp101Tyr) of the Cu/Zn superoxide dismutase (SOD1) gene. The disease started with a bulbar symptom (rapidly progressive hoarseness) and at autopsy showed degenerative changes restricted to the upper and lower motor neuron systems (more strictly, with lower motor predominance, showing the most severe degeneration in the nucleus ambiguus). Occasional intracytoplasmic Lewy-body-like hyaline inclusions that were immunoreactive for ubiquitin and SOD1, but immunonegative for neurofilament protein, were found in the lower motor neurons. This is the first report of hoarseness as the initial manifestation of FALS. This SOD1 gene mutation may be associated with a particular clinicopathological phenotype.