title: Familial amyotrophic lateral sclerosis with an I104F mutation in the SOD1 gene: Multisystem degeneration with neurofilamentous aggregates and SOD1 inclusions.
abstract: We previously reported familial amyotrophic lateral sclerosis (FALS) of 11 years duration in a 57-year-old woman, who received artificial ventilation for 5 years prior to death and exhibited widespread multisystem degeneration and neurofilamentous aggregates, so-called conglomerate inclusions (CIs). In the present study, we re-evaluated this autopsied patient (proband) with further immunohistochemical observation as well as mutational analysis of the superoxide dismutase 1 (SOD1) gene. A review of the clinical features of the proband's family revealed five affected members (including the proband) over two successive generations who showed marked variability in clinical presentation, such as the age at onset. The proband was found to harbor a heterozygous missense mutation in exon 4 (I104F) of the SOD1 gene. In the brain and spinal cord, SOD1-positive neuronal cytoplasmic inclusions (NCIs) were found to be more widely distributed than CIs, the latter being weakly positive for SOD1. No Lewy body-like hyaline inclusions were found. This is considered to be the first description of an autopsy case of FALS with an I104F SOD1 gene mutation, suggesting that combination of marked intra-familial clinical variability and multisystem degeneration with occurrence of CIs and SOD1-positive NCIs is a characteristic feature of FALS with this SOD1 gene mutation.
authors.affiliation: Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.|Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Haishan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Departments of Molecular Neuroscience, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiga
authors.affiliation: Departments of Neurology, Brain Research Institute, University of Niigata, Niigata, Japan.|Multiple Sclerosis Center, Utano National Hospital, Kyoto, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Departments of Molecular Neuroscience, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.affiliation: Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Departments of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D013116:Spinal Cord / Q000473:pathology*; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
chemical_list: C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
keywords: SOD1; familial amyotrophic lateral sclerosis; multiple system degeneration; neurofilament aggregate; prolonged survival