Abstract
Several missense mutations within exons 1, 2, 4 and 5 of the gene for Cu/Zn-binding superoxide dismutase (SOD1) have been discovered to be involved in the development of chromosome 21q-linked familial amyotrophic lateral sclerosis (FALS). We describe here an autopsied patient with FALS, in whom we have recently identified a novel missense mutation in exon 1 of the SOD1 gene. The neuropathological findings were compatible with those described previously in patients with FALS with posterior column involvement. This suggests that mutations of the SOD1 gene may be responsible for this form of FALS.
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Deng H-X, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung W-Y, Getzoff ED, Hu P, Herzfeldt B, Roos RP, Warner C, Deng G, Soriano E, Smyth C, Parge HE, Ahmed A, Roses AD, Hallewell RA, Pericak-Vance MA, Siddique T (1993) Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261: 1047–1051
Engel WK, Kurland LT, Klatzo I (1959) An inherited disease similar to amyotrophic lateral sclerosis with a pattern of posterior column invovement. An intermediate form? Brain 82: 203–220
Hirano A, Kurland LT, Sayre GP (1967) Familial amyotrophic lateral sclerosis. A subgroup characterized by posterior and spinocerebellar tract involvement and hyaline inclusions in the anterior horn cells. Arch Neurol 16: 232–243
Horton WA, Eldridge R, Brody JA (1976) Familial motor neuron disease. Evidence for at least three different types. Neurology 26: 460–465
Kato S, Hirano A (1992) Involvement of the brain stem reticular formation in familial amyotrophic lateral sclerosis. Clin Neuropathol 11: 41–44
Kato T, Hirano A, Kurland LT (1987) Asymmetric involvement of the spinal cord involving both large and small anterior horn cells in a case of familal amyotrophic lateral sclerosis. Clin Neuropathol 6: 67–70
Kubo H, Ikuta F, Tsubaki T (1967) An autopsy case with a history of familial amytrophic lateral sclerosis and posterior column involvement. Clin Neurol (Tokyo) 7: 45–51
Mizusawa H, Matsumoto S, Yen S-H, Hirano A, Rojas-Corona RR, Donnenfeld H (1989) Focal accumulation of phosphorylated neurofilaments within anterior horn cell in familial amyotrophic lateral sclerosis. Acta Neuropathol 79: 37–43
Mizusawa H, Hirano A, Yen S-H (1991) Anterior horn cell inclusions in familial amyotrophic lateral sclerosis contain ubiquitin and phosphorylated neurofilament epitopes. Neuropathology 11: 11–20
Mulder DW, Kurland LT, Offord KP, Beard CM (1986) Familial adult motor neuron disease: amyotrophic lateral sclerosis. Neurology 36: 511–517
Murayama S, Ookawa Y, Mori H, Nakano I, Ihara Y, Kuzuhara S, Tomonaga M (1989) Immunocytochemical and ultrastructural study of Lewy body-like hyaline inclusions in familial amyotrophic lateral sclerosis. Acta Neuropathol 78: 143–152
Nakano I, Hirano A, Kurland LT, Mulder DW, Holley PW, Saccomanno G (1984) Familial amyotrophic lateral sclerosis. Neuropathology of two brothers in American “C” family. Neurol Med (Tokyo) 20: 458–471
Nakano R, Sato S, Inuzuka T, Sakimura K, Mishina M, Takahashi H, Ikuta F, Honma Y, Fujii J, Taniguchi N, Tsuji S (1994) A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis. Biochem Biophys Res Commun 200: 695–703
Powers JM, Horoupian DS, Schaumburg HH (1974) Wetherbee Ail. Documentation of a neurological disease in a Vermont family 90 years later. Can J Neurol Sci 1: 139–140
Rewcastle NB (1991) Degenerative diseases of the central nervous system. In: Daves RL, Robertson DM (eds) Textbook of neuropathology, 2nd edn. Williams and Wilkins, Baltimore, pp 948–949
Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng H-X, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B, Van den Bergh R, Hung W-Y, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak-Vance MA, Haines J, Rouleau GA, Gusella JS, Horvitz HR, Brown RH Jr (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362: 59–62
Siddique T, Pericak-Vance MA, Brooks BR, Roos RP, Hung W-Y, Antel JP, Munsat TL, Phillips K, Warner K, Speer M, Bias WB, Siddique NA, Roses AD (1989) Linkage analyasis in familial amyotrophic lateral sclerosis. Neurology 39: 919–925
Siddique T, Figlewicz DA, Pericak-Vance MA, Haines JL, Rouleau G, Jeffers AJ, Sapp P, Hung W-Y, Bebout J, McKenna-Yasek D, Deng G, Horvitz HR, Gusella JF, Brown RH Jr, Roses AD (1991) Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med 324: 1381–1384
Takahashi H, Ikuta F (1992) Bunina body in amyotrophic lateral sclerosis. Brain Nerve (Tokyo) 44: 525–532
Takahashi K, Nakamura H, Okada E (1972) Hereditary amyotrophic lateral sclerosis. Histochemical and electron microscopic study of hyaline inclusions in motor neurons. Arch Neurol 27: 292–299
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Supported in part by a research grant for CNS degenerative discases from the Ministry of Health and Welfare, Japan
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Takahashi, H., Makifuchi, T., Nakano, R. et al. Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene. Acta Neuropathol 88, 185–188 (1994). https://doi.org/10.1007/BF00294513
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DOI: https://doi.org/10.1007/BF00294513