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Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11

Nature Genetics volume 8, pages 280–284 (1994)Cite this article

Abstract

Autosomal dominant ataxias are a genetically heterogeneous group of disorders for which spinocerebellar ataxia (SCA) loci on chromosomes 6p, 12q, 14q and 16q have been reported. We have examined 170 individuals (56 of whom were affected) from a previously unreported ten-generation kindred with a dominant ataxia that is clinically and genetically distinct from those previously mapped. The family has two major branches which both descend from the paternal grandparents of President Abraham Lincoln. Among those examined, 56 individuals have a generally non-life threatening cerebellar ataxia. Disease onset varies from 10–68 years and anticipation is evident. We have mapped this gene, spinocerebellar ataxia type 5 (SCA5), to the centromeric region of chromosome 11

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References

  1. Harding, A.E. The clinical features and classification of the late onset autosomal dominant cerebellar ataxia: a study of 11 families, including descendants of ‘The Drew Family of Walworth’. Brain 105, 1–28 (1982).

    Article  CAS  PubMed  Google Scholar 

  2. Zoghbi, H.Y. The spinocerebellar degenerations. Curr. Neurol. 11, 121–144 (1991).

    Google Scholar 

  3. Schut, J.W. Hereditary ataxia: Clinical study through six generations. Archs. Neurol. Psychiat. 63, 535–586 (1950).

    Article  Google Scholar 

  4. Nino, H.E. et al. A family with hereditary ataxia: HLA typing. Neurology 3O, 12–20(1980).

    Article  Google Scholar 

  5. Haines, J.L., Schut, L.J., Weitkamp, L.R., Thayer, M. & Anderson, V.E Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies. Neurology 34, 1542–1548 (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Zoghbi, H.Y. et al. Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred. Ann. Neurol. 23, 580–584 (1988).

    Article  CAS  PubMed  Google Scholar 

  7. Orozco Diaz, G., Nodarse Fleites, A., Cordoves Sagaz, 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  CAS  PubMed  Google Scholar 

  8. Barbeau, A. et al. The natural history of Machado-Joseph disease An analysis of 138 personally examined cases. Can. J. neurol. Sci. 11, 510–525 (1984).

    Article  CAS  PubMed  Google Scholar 

  9. Rosenberg, R.N. Machado-Joseph disease: an autosomal dominant system degeneration. Mov. Dis. 7, 193–203 (1992).

    Article  CAS  Google Scholar 

  10. 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 

  11. Ranum, L.P.W. et al. Localization of the autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) locus, in two kindreds within an 8-cM subregion of chromosome 6p. Am. J. hum. Genet. 49, 31–41 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Zoghbi, H.Y. et al. The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds. Am. J. hum. Genet. 49, 23–30(1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kwiatkowski, T.J. Jr., et al. The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps centromeric to D6S89 and shows no recombination, in nine large kindreds, with a dinucleotide repeat at the AM10 locus. Am. J. hum. Genet. 53, 391–400 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Gispert, S. et al. Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23–24.1. Nature Genet. 4, 295–299(1993).

    Article  CAS  PubMed  Google Scholar 

  15. Takiyama, Y. et al. The gene for Machado-Joseph disease maps to human chromosome 14q. Nature Genet. 4, 300–304 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Stevanin, G. et al. A third locus for autosomal dominant cerebellar ataxia type 1 maps to chromosome 14q24.3–qter: evidence for the existence of a fourth locus. Am. J. hum. Genet. 54 11–20 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Gardner, K. et al. Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. Neurology 44, A361 (1994).

    Article  Google Scholar 

  18. Orr, H.T. et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nature Genet. 4, 211–226 (1993).

    Article  Google Scholar 

  19. Ranum, L. et al. Molecular and clinical correlations in spinocerebellar ataxia type I (SCA1): evidence for familial effects on the age at onset. Am. J. hum. Genet. 55, 244–252 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Jodice, C. et al. Effect of trinucleotide repeat length and parental sex onphenotypic variation in spinocerebellar ataxia. Arn. J. hum. Genet. 54, 959–965(1994).

    CAS  Google Scholar 

  21. Kremer, E.J. et al. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n . Science 252, 1711–1714 (1991).

    Article  CAS  PubMed  Google Scholar 

  22. Verkerk, A.J.M.H. et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 65, 905–914 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. Fu, Y.-H. et al. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Cell 67, 1047–1058 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Knight, S. et al. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell 74, 127–134 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. La Spada, A.R., Wilson, E.M., Lubahn, D.B., Hardin, A.E. & Fischback, K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79 (1991).

    Article  CAS  PubMed  Google Scholar 

  26. Fu, Y.-H. et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67, 1047–1058 (1992).

    Article  Google Scholar 

  27. Harley, H.G. et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 355, 545–546 (1992).

    Article  CAS  PubMed  Google Scholar 

  28. Mahadevan, M. et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255, 1253–1255 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Huntington's disease collaborative research group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971–983 (1993).

    Article  Google Scholar 

  30. Koide, R. et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nature Genet. 6, 9–13 (1994).

    Article  CAS  PubMed  Google Scholar 

  31. Nagafuchi, S. et al. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nature Genet. 6, 14–18(1994).

    Article  CAS  PubMed  Google Scholar 

  32. Burke, J. et al. The Haw-River Syndrome: Dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nature Genet. 7, 521–524 (1994).

    Article  CAS  PubMed  Google Scholar 

  33. Hoffman, P.M., Stuart, W.H., Earle, K.M. & Brody, J.A. Hereditary late-onset cerebellar degeneration. Neurology 21, 771–777 (1971).

    Article  Google Scholar 

  34. Frontali, M. et al. Autosomal dominant pure cerebellar ataxia: neurological and genetic study. Brain 115, 1647–1654 (1992).

    Article  PubMed  Google Scholar 

  35. Buetow, K.H. et al. Integrated human genome-wide maps constructed using the CEPH reference panel. Nature Genet. 6, 391–396 (1994).

    Article  CAS  PubMed  Google Scholar 

  36. Terwilliger, J. & Ott, J. Handbook of human genetic linkage (Johns Hopkins University Press, Baltimore, 1994).

    Google Scholar 

  37. 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 

  38. Chung, M.-Y., Ranum, L.P.W., Duvick, L.A., Servadio, A., Zoghbi, H.Y. & Orr, H.T. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type 1. Nature Genet. 5, 254–258 (1993).

    Article  CAS  PubMed  Google Scholar 

  39. Bell, G.I., Kavam, J. & Putter, W. Polymorphic DNA region adjacent to the 5′ end of the human insulin gene. Proc. natn. Acad. Sci U.S.A. 78, 5759–5763 (1981).

    Article  CAS  Google Scholar 

  40. Weber, J.L. et al. Evidence for human meiotic recombination interference obtained through construction of a short tandem repeat-polymorphism linkage map of chromosome 19. Am. J. hum. Genet. 53, 1079–1095 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Gyapay, G. et al. The 1993–94 Genethon human genetic linkage map. Nature Genet. 7, 246–339 (1994).

    Article  CAS  PubMed  Google Scholar 

  42. 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 

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Authors and Affiliations

  1. Department of Neurology, University of Minnesota, 420 Delaware Street, S.E., Minneapolis, Minnesota, 55455, USA

    Laura P.W. Ranum, Lawrence J. Schut & Julie K. Lundgren

  2. Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, S.E., Minneapolis, Minnesota, 55455, USA

    Julie K. Lundgren & Harry T. Orr

  3. Department of Biochemistry, University of Minnesota, 420 Delaware Street, S.E., Minneapolis, Minnesota, 55455, USA

    Harry T. Orr & Dennis M. Livingston

  4. The Institute of Human Genetics, University of Minnesota, 420 Delaware Street, S.E., Minneapolis, Minnesota, 55455, USA

    Harry T. Orr

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  1. Laura P.W. Ranum
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Ranum, L., Schut, L., Lundgren, J. et al. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet 8, 280–284 (1994). https://doi.org/10.1038/ng1194-280

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