title: Familial amyotrophic lateral sclerosis. Molecular pathology of a patient with a SOD1 mutation.
abstract: We report the clinical, genetic, and neuropathologic findings in a patient with rapidly progressive familial amyotrophic lateral sclerosis (ALS). We detected a point mutation at codon 48 of the Cu/Zn superoxide dismutase gene (SOD1) leading to a substitution of histidine by glutamine in the copper-binding domain. The histopathologic features are consistent with those described in rapidly progressive sporadic ALS and do not support claims that sporadic and familial disease are different pathologic entities. Neurofilamentous accumulations, hyaline, and ubiquitinated inclusions were present in the motor cortex, brainstem, and anterior horn cells, but there was no evidence of abnormal SOD1 immunoreactivity. This confirms that the cytoskeletal pathology specific to ALS is secondary to an unknown biochemical disturbance caused by mutant SOD1 molecules and not its toxic accumulation.
authors.affiliation: Department of Clinical Neuroscience, Institute of Psychiatry, London, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Shaw
authors.forename: Z E
authors.initials: ZE
authors.lastname: Enayat
authors.forename: J F
authors.initials: JF
authors.lastname: Powell
authors.forename: V E
authors.initials: VE
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Radunovic
authors.forename: S
authors.initials: S
authors.lastname: al-Sarraj
authors.forename: P N
authors.initials: PN
authors.lastname: Leigh
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008854:Microscopy, Electron; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D013482:Superoxide Dismutase