title: Familial amyotrophic lateral sclerosis with bulbar onset and a novel Asp101Tyr Cu/Zn superoxide dismutase gene mutation.
abstract: 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.
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, 951-8585 Niigata, Japan.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Tan
authors.forename: Yue-Shan
authors.initials: YS
authors.lastname: Piao
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Obata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Umeda
authors.forename: Masahisa
authors.initials: M
authors.lastname: Sato
authors.forename: Takao
authors.initials: T
authors.lastname: Fukushima
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nakano
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006685:Hoarseness / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D009154:Mutation; D009410:Nerve Degeneration / Q000473:pathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*; D014826:Vocal Cord Paralysis / Q000209:etiology
chemical_list: D013482:Superoxide Dismutase