Abstract
We screened 217 patients from Germany (n = 213), Austria (n = 2) and Switzerland (n = 2) with a positive family history for amyotrophic lateral sclerosis (ALS) for mutations in the copper/zinc superoxide dismutase (SOD1) gene. We found that 13% of the families tested carried mutations. By analyzing inheritance, we detected a clear-cut co-segregation in 5 of the 28 families; however, in two families with an established mutation, co-segregation was absent. In Germany, the R115G mutation is comparatively frequent and exhibits a specific aggressive phenotype. The L144F mutation, which is the most prevalent mutation in the Balkan countries, and the D90A mutation which is the most frequent SOD1 mutation globally, seem to be the second most common disease-causing mutations in Germany.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abe K, Aoki M, Ikeda M, Watanabe M, Hirai S, Itoyama Y (1996) Clinical characteristics of familial amyotrophic lateral sclerosis with Cu/Zn superoxide dismutase gene mutations. J Neurol Sci 136:108–116
Andersen PM, Nilsson P, Ala-Hurula V, Keranen ML, Tarvainen I, Haltia T, Nilsson L, Binzer M, Forsgren L, Marklund SL (1995) Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat Genet 10:61–66
Andersen PM, Sims KB, Xin WW, Kiely R, O’Neill G, Ravits J, Pioro E, Harati Y, Brower RD, Levine JS, Heinicke HU, Seltzer W, Boss M, Brown RH Jr (2003) Sixteen novel mutations in the Cu/Zn superoxide dismutase gene in amyotrophic lateral sclerosis: a decade of discoveries, defects and disputes. Amyotroph Lateral Scler Other Motor Neuron Disord 4:62–73
Andersen PM (2006) Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Curr Neurol Neurosci Rep 6:37–46
Aoki M, Ogasawara M, Matsubara Y, Narisawa K, Nakamura S, Itoyama Y, Abe K (1993) Mild ALS in Japan associated with novel SOD mutation. Nat Genet 5:323–324
Ceroni M, Malaspina A, Poloni TE, Alimonti D, Rognoni F, Habgood J, Imbesi F, Antonelli P, Alfonsi E, Curti D, deBelleroche J (1999) Clustering of ALS patients in central Italy due to the occurrence of the L84F SOD1 gene mutation. Neurology 53:1064–1071
Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt B, Roos RP (1993) Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261:1047–1051
Figlewicz DA, Orrell RW (2003) The genetics of motor neuron diseases. Amyotroph Lateral Scler Other Motor Neuron Disord 4:225–231
Hand CK, Mayeux-Portas V, Khoris J, Briolotti V, Clavelou P, Camu W, Rouleau GA (2001) Compound heterozygous D90A and D96N SOD1 mutations in a recessive amyotrophic lateral sclerosis family. Ann Neurol 49:267–271
Jonsson PA, Backstrand A, Andersen PM, Jacobsson J, Parton M, Shaw C, Swingler R, Shaw PJ, Robberecht W, Ludolph AC, Siddique T, Skvortsova VI, Marklund SL (2002) CuZn-superoxide dismutase in D90A heterozygotes from recessive and dominant ALS pedigrees. Neurobiol Dis 10:327–333
Kostrzewa M, Burck-Lehmann U, Muller U (1994) Autosomal dominant amyotrophic lateral sclerosis: a novel mutation in the Cu/Zn superoxide dismutase-1 gene. Hum Mol Genet 3:2261–2262
Kostrzewa M, Damian MS, Muller U (1996) Superoxide dismutase 1: identification of a novel mutation in a case of familial amyotrophic lateral sclerosis. Hum Genet 98:48–50
Niemann S, Joos H, Meyer T, Vielhaber S, Reuner U, Gleichmann M, Dengler R, Muller U (2004) Familial ALS in Germany: origin of the R115G SOD1 mutation by a founder effect. J Neurol Neurosurg Psychiatry 75:1186–1188
Pramatarova A, Figlewicz DA, Krizus A, Han FY, Ceballos-Picot I, Nicole A, Dib M, Meininger V, Brown RH, Rouleau GA (1995) Identification of new mutations in the Cu/Zn superoxide dismutase gene of patients with familial amyotrophic lateral sclerosis. Am J Hum Genet 56:592–596
Robberecht W, Aguirre T, Van den Bosch L, Tilkin P, Cassiman JJ, Matthijs G (1996) D90A heterozygosity in the SOD1 gene is associated with familial and apparently sporadic amyotrophic lateral sclerosis. Neurology 47:1336–1339
Rosen DR (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 364:362
Shaw CE, Enayat ZE, Chioza BA, Al-Chalabi A, Radunovic A, Powell JF, Leigh PN (1998) Mutations in all five exons of SOD-1 may cause ALS. Ann Neurol 43:390–394
Siddique T, Figlewicz DA, Pericak-Vance MA, Haines JL, Rouleau G, Jeffers AJ, Sapp P, Hung WY, Bebout J, McKenna-Yasek D (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
Siddique T, Nijhawan D, Hentati A (1996) Molecular genetic basis of familial ALS. Neurology 47:S27–S34
Valentine JS, Doucette PA, Zittin Potter S (2005) Copper–zinc superoxide dismutase and amyotrophic lateral sclerosis. Annu Rev Biochem 74:563–593
Winter SM, Claus A, Oberwittler C, Volkel H, Wenzler S, Ludolph AC (2000) Recessively inherited amyotrophic lateral sclerosis: a Germany family with the D90A CuZn-SOD mutation. J Neurol 247:783–786
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00415-010-5572-x
Rights and permissions
About this article
Cite this article
Rabe, M., Felbecker, A., Waibel, S. et al. The epidemiology of CuZn-SOD mutations in Germany: a study of 217 families. J Neurol 257, 1298–1302 (2010). https://doi.org/10.1007/s00415-010-5512-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-010-5512-9