Summary
Both autosomal dominant olivo-ponto-cerebellar atrophy (OPCA) and Holmes' ataxia are the progressive neurodegenerative disorders of adulthood with unknown biochemical defects. In order to determine the genetic locus and possible genetic heterogeneity, linkage study was performed in 19 OPCA families comprising 180 individuals with 60 affected patients, and two Holmes' ataxia families comprising 39 individuals with 10 affected patients. By using computer program LIPED, linkage of each disorder was analyzed to 12 blood groups, 5 red cell enzymes, HLA-A, −B, −C, and F13A. No evidence suggesting linkage to these two disorders was obtained in the markers examined, including three 6p markers such as HLA, GLO1, and F13A. Furthermore, in 14 out of 15 HLA-informative OPCA families, negative lod scores for OPCA with HLA were obtained at most recombination fractions. Our results provide further evidence suggesting the genetic heterogeneity of dominant OPCA.
Similar content being viewed by others
Article PDF
References
Board, P.G. 1979. Genetic polymorphism of the A subunit of human coagulating factor XIII.Am. J. Hum. Genet. 31: 116–124.
Fujii, M., Fukatsu, R., Takahata, N., and Kawata, H. 1987. A unique family of hereditary ataxia: clinico-pathological study of an autopsied case (Japanese abstract).Clin. Neurol. (Tokyo) 27: 781.
Haines, J.L., Schut, L.J., Weikamp, L.R., Thayer, M., and Anderson, E. 1984. Spinocerebellar ataxia in a large kindred: age at onset, reproduction, and genetic linkage studies.Neurology (Cleveland) 34: 1542–1548.
Haines, J.L. and Trofatter, J.A. 1986. Multipoint linkage analysis of spinocerebellar ataxia and markers on chromosome 6.Genet. Epidemiol. 3: 399–405.
Harding, A.E. 1984. Autosomal dominant cerebellar ataxia. InThe Hereditary Ataxias and Related Disorders, Churchill Livingstone, New York, pp. 129–165.
Harris, H. and Hopkinson, D.A. 1976.Handbook of Enzyme Electrophoresis in Human Genetics, North-Holland, Oxford.
Jackson, J.F., Currier, R.D., Terasaki, P.I., and Morton, N.E. 1977. Spinocerebellar ataxia and HLA linkage.N. Engl. J. Med. 296: 1138–1141.
Jackson, J.F., Whittington, J.E., Currier, R.D., Terasaki, P., Morton, N.E., and Keats, B.J. 1978. Genetic linkage and spinocerebellar ataxia.Adv. Neurol. 21: 315–318.
Kanazawa, I., Yoshizawa, K., Kondo, I., and Ikemoto, S. 1987. The dominantly inherited spinocerebellar ataxia (SCA1) locus maps distally from HLA on chromosome 6.Cytogenet. Cell Genet. 46: 636 (HGM9 abstract).
Koeppen, A.H., Goedde, H.W., Hiller, C., Hirth, L., and Benkmann, H.-G. 1981. Hereditary ataxia and the sixth chromosome.Arch. Neurol. 38: 158–164.
Kudoh, J., Ikeda, T., and Takahata, N. 1986. A clinico-pathological study of slow saccades and sleep disturbances—Two autopsy cases with hereditary spinocerebellar degeneration.Clin. Neurol. (Tokyo) 26: 601–611.
Kumar, D., Blank, C.E., and Gelsthorpe, K. 1986. Hereditary cerebellar ataxia and genetic linkage with HLA.Hum. Genet. 72: 327–332.
Landis, D.M.D., Rosenberg, R.N., Landis, S.C., Schut, L., and Nyhan, W.L. 1974. Olivoponto-cerebellar degeneration. Clinical and ultrastructural abnormalities.Arch. Neurol. 31: 295–307.
Möller, E., Hindfelt, B., and Olsson, J.-E. 1978. HLA-determination in families with hereditary ataxia.Tissue Antigens 12: 357–366.
Morton, N.E., Lalouel, J.-M., Jackson, J.F., Currier, R.D., and Yee, S. 1980. Linkage studies in spinocerebellar ataxia (SCA).Am. J. Med. Genet. 6: 251–257.
Nino, H.E., Noreen, H.J., Dubey, D.P., Resch, J.A., Namboodiri, K., Elston, R.C., and Yunis, E. 1980. A family with hereditary ataxia: HLA typing.Neurology (N.Y.) 3: 12–20.
Nishigaki, T., Tokunaga, K., Ishii, C., Omoto, K., Akaza, T., Akiyama, N., Juji, T., Murata, S., Naito, S., Saji, H., Satoh, H., Shiraki, T., Tokunaga, K., and Yasuda, N. 1986. No evidence for linkage between the loci for coagulating factor XIII-A and HLA.Hum. Genet. 72: 266–267.
Olaisen, B., Sakaguchi, A., and Naylor, S.L. 1987. Report of the committee on the genetic constitution of chromosome 5 and 6.Cytogenet. Cell Genet. 46: 147–169.
Ott, J. 1974. Estimation of the recombination fraction in human pedigrees: Efficient computation of the likelihood for human linkage studies.Am. J. Hum. Genet. 26: 588–597.
Ott, J. 1978. A simple scheme for the analysis of HLA linkages in pedigrees.Ann. Hum. Genet. 42: 255–257.
Ott, J. 1985. Few large or many small families? InAnalysis of Human Genetic Linkage, The Johns Hopkins University Press, Baltimore, p. 55.
Pedersen, L., Platz, P., Ryder, L.P., Lamm, L.U., and Dissing, J. 1980. A linkage study of hereditary ataxias and related disorders. Evidence of heterogeneity of dominant cerebellar ataxia.Hum. Genet. 54: 371–383.
Rich, S.S., Wilkie, P., Shut, L., Vance, G., and Orr, H.T. 1987. Spinocerebellar ataxia: Localization of an autosomal dominant locus between two markers on human chromosome 6.Am. J. Hum. Genet. 41: 524–531.
Rosenberg, R.N. 1986. Spinocerebellar degenerations. InNeurogenetics. Principles and Fractice, Raven Press, New York, pp. 109–134.
Schut, C.J.W. 1950. Hereditary ataxia. Clinical study through six generations.Arch. Neurol. Psychiat. 63: 535–568.
Schut, C.J.W. 1951. Hereditary ataxia. A survey of certain clinical, pathological and genetic features with linkage data on five additional hereditary factors.Am. J. Hum. Genet. 3: 93–110.
Wastiaux, J.P., Lamoureux, G., Bouchard, J.P., Durivage, A., Barbeau, C., and Barbeau, A. 1978. HLA and complement typing in olivo-ponto-cerebellar atrophy.Can. J. Neurol. Sci. 5: 75–81.
Whittington, J.E., Keats, B.J.B., Jackson, J.F., Currier, R.D., and Terasaki, P.I. 1980. Linkage studies on glyoxalase I (GLO), pepsinogen (PG), spinocerebellar ataxia (SCA1), and HLA.Cytogenet. Cell Genet. 28: 145–150.
Wilkie, P., Rich, S., Schut, L., and Orr, H. 1987. Spinocerebellar ataxia: localization of the autosomal dominant HLA-linked form between two markers on human chromosome 6.Cytogenet. Cell Genet. 46: 715 (HGM9 abstract).
Wong, P., Komarnicki, L., Schroeder, M.L., Lewis, M., Kaita, H., Philipps, S., Stranc, L., and McAlpine, P.J. 1988. Analysis for linkage between F13A and three chromosome 6 marker loci: evidence for 6pter:F13A:HLA:GLO1:cen gene order.Hum. Genet. 79: 228–230.
Yakura, H., Wakisaka, A., Fujimoto, S., and Itakura, K. 1974. Hereditary ataxia and HL-A genotypes.N. Engl. J. Med. 291: 154–155.
Zoghbi, H.Y., Pollack, M.S., Ferrell, R.E., Daiger, S.P., Lyons, L.A., O'Brien, W.E., and Beaudet, A.L. 1987. Linkage studies in spinocerebellar ataxia (SCA1).Cytogenet. Cell Genet. 46: 727 (HGM9 abstract).
Zoghbi, H.Y., Pollack, M.S., Lyons, L.A., Ferrell, R.E., Daiger, S.P., and Beaudet, A.L. 1988. Spinocerebellar ataxia: variable age of onset and linkage to human leukocyte antigen in a large kindred.Ann. Neurol. 23: 580–584.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sasaki, H., Wakisaka, A., Katoh, T. et al. Linkage study of dominantly inherited olivo-ponto-cerebellar atrophy (OPCA) and holmes' ataxia. Jap J Human Genet 33, 423–438 (1988). https://doi.org/10.1007/BF01897783
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01897783