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. 1995 Mar;56(3):592–596.

Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis.

A Pramatarova 1, D A Figlewicz 1, A Krizus 1, F Y Han 1, I Ceballos-Picot 1, A Nicole 1, M Dib 1, V Meininger 1, R H Brown 1, G A Rouleau 1
PMCID: PMC1801158  PMID: 7887412

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting motor neurons. Although most cases of ALS are sporadic, approximately 10% are inherited as an autosomal dominant trait. Mutations in the Cu/Zn superoxide dismutase gene (SOD 1) are responsible for a fraction of familial ALS (FALS). Screening our FALS kindreds by SSCP, we have identified mutations in 15 families, of which 9 have not been previously reported. Two of the new mutations alter amino acids that have never been implicated in FALS. One of them affects a highly conserved amino acid involved in dimer contact, and the other one affects the active-site loop of the enzyme. These two mutations reduce significantly SOD 1 enzyme activity in lymphoblasts. Our results suggest that SOD 1 mutations are responsible for > or = 13% of FALS cases.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aoki M., Ogasawara M., Matsubara Y., Narisawa K., Nakamura S., Itoyama Y., Abe K. Mild ALS in Japan associated with novel SOD mutation. Nat Genet. 1993 Dec;5(4):323–324. doi: 10.1038/ng1293-323. [DOI] [PubMed] [Google Scholar]
  2. Bannister W. H., Bannister J. V., Barra D., Bond J., Bossa F. Evolutionary aspects of superoxide dismutase: the copper/zinc enzyme. Free Radic Res Commun. 1991;12-13 Pt 1:349–361. doi: 10.3109/10715769109145804. [DOI] [PubMed] [Google Scholar]
  3. Coyle J. T., Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993 Oct 29;262(5134):689–695. doi: 10.1126/science.7901908. [DOI] [PubMed] [Google Scholar]
  4. Deng H. X., Hentati A., Tainer J. A., Iqbal Z., Cayabyab A., Hung W. Y., Getzoff E. D., Hu P., Herzfeldt B., Roos R. P. Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science. 1993 Aug 20;261(5124):1047–1051. doi: 10.1126/science.8351519. [DOI] [PubMed] [Google Scholar]
  5. Elshafey A., Lanyon W. G., Connor J. M. Identification of a new missense point mutation in exon 4 of the Cu/Zn superoxide dismutase (SOD-1) gene in a family with amyotrophic lateral sclerosis. Hum Mol Genet. 1994 Feb;3(2):363–364. doi: 10.1093/hmg/3.2.363. [DOI] [PubMed] [Google Scholar]
  6. Getzoff E. D., Tainer J. A., Weiner P. K., Kollman P. A., Richardson J. S., Richardson D. C. Electrostatic recognition between superoxide and copper, zinc superoxide dismutase. Nature. 1983 Nov 17;306(5940):287–290. doi: 10.1038/306287a0. [DOI] [PubMed] [Google Scholar]
  7. Levanon D., Lieman-Hurwitz J., Dafni N., Wigderson M., Sherman L., Bernstein Y., Laver-Rudich Z., Danciger E., Stein O., Groner Y. Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase. EMBO J. 1985 Jan;4(1):77–84. doi: 10.1002/j.1460-2075.1985.tb02320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Marklund S., Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974 Sep 16;47(3):469–474. doi: 10.1111/j.1432-1033.1974.tb03714.x. [DOI] [PubMed] [Google Scholar]
  9. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  10. Pramatarova A., Goto J., Nanba E., Nakashima K., Takahashi K., Takagi A., Kanazawa I., Figlewicz D. A., Rouleau G. A. A two basepair deletion in the SOD 1 gene causes familial amyotrophic lateral sclerosis. Hum Mol Genet. 1994 Nov;3(11):2061–2062. [PubMed] [Google Scholar]
  11. Rainero I., Pinessi L., Tsuda T., Vignocchi M. G., Vaula G., Calvi L., Cerrato P., Rossi B., Bergamini L., McLachlan D. R. SOD1 missense mutation in an Italian family with ALS. Neurology. 1994 Feb;44(2):347–349. doi: 10.1212/wnl.44.2.347. [DOI] [PubMed] [Google Scholar]
  12. Rosen D. R., Siddique T., Patterson D., Figlewicz D. A., Sapp P., Hentati A., Donaldson D., Goto J., O'Regan J. P., Deng H. X. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59–62. doi: 10.1038/362059a0. [DOI] [PubMed] [Google Scholar]
  13. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  14. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Siddique T., Figlewicz D. A., Pericak-Vance M. A., Haines J. L., Rouleau G., Jeffers A. J., Sapp P., Hung W. Y., Bebout J., McKenna-Yasek D. Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med. 1991 May 16;324(20):1381–1384. doi: 10.1056/NEJM199105163242001. [DOI] [PubMed] [Google Scholar]
  16. Tandan R., Bradley W. G. Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management. Ann Neurol. 1985 Sep;18(3):271–280. doi: 10.1002/ana.410180302. [DOI] [PubMed] [Google Scholar]

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