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Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23–24.1

Abstract

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders characterized by onset with gait ataxia, dysarthria, dysmetria and dysdiadochokinesia. We have demonstrated previously genetic heterogeneity within these disorders by excluding the disease locus from the documented spinocerebellar ataxia locus (SCA1) on chromosome 6p in a large Cuban founder population. We now report the assignment of a second locus for ADCA (SCA2) to chromosome 12q23–24.1 following linkage analyses carried out for the Cuban pedigrees, with probable flanking markers D12S58 and phospholipase A2. Investigation of linkage to the interval containing SCA2 for seven French ADCA families, previously excluded from linkage to SCA1, provides preliminary data suggesting the existence of a third ADCA locus (SCA3).

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References

  1. Weatherall, D.J. The New Genetics and Clinical Practice (Oxford University Press, Oxford 1984).

    Google Scholar 

  2. Pogacar, S. et al. Dominant spino–pontine atrophy: Report of two additional members of the family W. Arch. Neurol. 35, 156–162 (1978).

    Article  CAS  PubMed  Google Scholar 

  3. Brown, S. On hereditary ataxy, with a series of twenty-one cases. Brain 15, 250–268 (1982).

    Article  Google Scholar 

  4. Konigsmark, B.W. & Lipton, H.L. Dominant olivo–ponto–cerebellar atrophy with extrapyramidal signs. Report of a family through three generations. Birth Defects Orig. Art. Ser. 1, 178–191 (1971).

    Google Scholar 

  5. Weiner, L.P., Konigsmark, B.W., Stoll, J. Jr. & Magladery, J.W. Hereditary olivo–ponto–cerebellar atrophy with retinal degeneration. Report of a family through six generations. Arch. Neurol. 16, 364–376 (1967).

    Article  CAS  PubMed  Google Scholar 

  6. Collins, F.S. Positional cloning: Let's not call it reverse anymore. Nature Genet. 1, 3–6 (1992).

    Article  CAS  PubMed  Google Scholar 

  7. Yakura, H., Wakisaka, A., Fujimotos, S. & Itakura, K. Hereditary ataxia and HLA genotypes. New Engl. J. Med. 291, 154–155 (1974).

    CAS  PubMed  Google Scholar 

  8. Jackson, J.F., Currier, R.D., Terasaki, P.I. & Morton, N.E. Spinocerebellar ataxia and HLA linkage: Risk prediction by HLA typing. New Engl. J. Med. 296, 1138–1141 (1977).

    Article  CAS  PubMed  Google Scholar 

  9. Litt, M. & Luty, J.A. Dinucleotide polymorphism at the D6S89 locus. Nucl. Acids Res. 18, 4301 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ranum, L., Chung, M.Y., Duvick, L.A., Zoghbi, H.Y. & Orr, H.T. Dinucleotide repeat polymorphism at the D6S109 locus. Nucl. Acids Res. 19, 1171 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Orozco, G., Nodarse, A., Cordoves, R. & Auburger, G. Autosomal dominant cerebellar ataxia: Clinical analysis of 263 patients from a homogeneous population in Holguin, Cuba. Neurology 40, 1369–1375 (1990).

    Article  Google Scholar 

  12. Auburger, G. et al. Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a Cuban founder effect population. Am. J. hum. Genet. 46, 1163–1177 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Keats, B.J.B. et al. Guidelines for human linkage maps: An international system for human linkage maps (ISLM, 1990). Genomics 9, 557–560 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Hoppener, J.W. et al. The human gene encoding insulin–like growth factor I is located on chromosome 12. Hum. Genet. 69, 157–160 (1985).

    Article  CAS  PubMed  Google Scholar 

  15. Weber, J.L., Kwitek, A.E., May, P.E., Wilkie, P.J. & Decker, R.A. In Human Gene Mapping 11. Report of the committee on the genetic constitution of chromosome 12. Cytogenet. cell Genet. 58, 555–579 [A26934] (1991).

    Google Scholar 

  16. Romanul, F.C.A., Fowler, H.L., Radvany, J., Feldman, R.G. & Feingold, M. Azorean disease of the nervous system. New Engl. J. Med. 296, 1505–1508 (1977).

    Article  CAS  PubMed  Google Scholar 

  17. Coutinho, P. & Andrade, C. Autosomal dominant system degeneration in Portuguese families of the Azores Islands: A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurol. 28, 703–709 (1978).

    Article  CAS  Google Scholar 

  18. Gispert, S., Nothers, C., Orozco, G. & Auburger, G. Search of the chromosome locus of autosomal dominant cerebellar ataxia from Holguin, Cuba: Exclusion from candidate regions on chromosome 4 and 11q. Hum. Heredity 43, 12–30 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Khati, C. et al. Genetic heterogeneity of autosomal dominant cerebellar ataxia type 1. Clinical and genetic analysis of 10 French families. Neurology (in the press).

  20. Weber, J.L. & May, P.E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. hum. Genet. 44, 388–396 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

    Article  CAS  Google Scholar 

  22. Ott, J. Genetic linkage studies in man. Transplant. Proc. XI, 1689–91 (1979).

    Google Scholar 

  23. Polymeropoulos, M.H., Rath, D.S., Xiao, H. & Merril, C.R. Trinucleotide repeat polymorphism at the human pancreatic phospholipase A-2 gene (PLA2). Nucl. Acids Res. 18, 7468 (1990).

    PubMed  PubMed Central  Google Scholar 

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Gispert, S., Twells, R., Orozco, G. et al. Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23–24.1. Nat Genet 4, 295–299 (1993). https://doi.org/10.1038/ng0793-295

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