title: Familial amyotrophic lateral sclerosis with a two base pair deletion in superoxide dismutase 1: gene multisystem degeneration with intracytoplasmic hyaline inclusions in astrocytes.
abstract: We performed a comparative neuropathological study on two siblings with familial amyotrophic lateral sclerosis (FALS). The clinical course of the sister who died at age 46 was 18 months, and that of the brother who died at age 65, 11 years. The neuropathological findings of the female were compatible with FALS with posterior column involvement. Her brother had multisystem degeneration in addition to the motor neuron disturbance; Lewy body-like hyaline inclusions (LBHIs) were present in the affected neurons of the degenerative lesions. Eosinophilic inclusions were seen in many astrocytes of the affected areas of the male FALS patient. Immunohistochemical assays revealed that most astrocytic inclusions reacted with the antibodies against Cu/Zn-superoxide dismutase 1 (SOD1) and ubiquitin; immunoreactivity was essentially the same as that of the neuronal LBHIs. Ultrastructurally the astrocytic inclusions were composed mainly of 15- to 25-nm granule-coated fibrils and granular material, resembling LBHIs of the neurons. Despite the dissimilar neuropathological features, both patients had the same two base pair deletion in exon 5 of the SOD1 gene. These findings suggest that FALS due to an SOD1 gene mutation is potentially a multisystem degenerative disorder, affecting not only neurons, but also astrocytes.
authors.affiliation: Division of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Shimoda
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Nakashima
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Ohama
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D001253:Astrocytes / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology; D003593:Cytoplasm / Q000737:chemistry; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005911:Gliosis / Q000473:pathology; D006801:Humans; D006818:Hyalin; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009410:Nerve Degeneration / Q000235:genetics; D009474:Neurons / Q000473:pathology; D009679:Nuclear Family; D009929:Organ Size; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: D013482:Superoxide Dismutase