Skip to main content
SpringerLink
Log in

A linkage study of hereditary ataxias and related disorders

Evidence of heterogeneity of dominant cerebellar ataxia

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Genetic markers controlled by 21 genetic systems were studied in 13 families containing members suffering from various hereditary disorders involving ataxia. Classical cerebellar ataxia was present in four, Friedreich ataxia in two, hereditary spastic paraplegia in four, and the Charcot-Marie-Tooth syndrome in three families. In each family, every available member above the lowest age at onset observed in that family, was subjected to a thorough clinical investigation and blood was sampled for investigation of genetic markers.

The families with cerebellar ataxia and with Charcot-Marie-Tooth syndrome contained enough informative relatives to allow a formal linkage study using the lodscore method. Three of the pedigress with cerebellar ataxia gave evidence of linkage between the disease and the HLA system with a combined lodscore of 2.128 at a recombination fraction θ of 0.05 for both sexes combined. The recombination fraction was considerably higher in females than in males, although the difference between the two sexes was not statistically significant.

Negative lodscores were obtained for the remaining family with cerebellar ataxia, which might be due to the fact that this family only provided information on recombination in females. However, the clinical features in this family differed from those in the other three families by a significantly higher frequency of dementia and pyramidal tract lesions. Based on these observations and on contradictory results in the literature concerning linkage between cerebellar ataxia and HLA, we suggest that there are two forms of cerebellar ataxia: One (CA1) linked to HLA with symptoms restricted to lesions in the cerebellum and spinocerebellar system and another (CA2) not linked to HLA with symptoms from more wide-spread lesions of the CNS.

None of the other genetic markers (except perhaps GLO) showed linkage to the cerebellar ataxias. Negative lodscores throughout with all 21 genetic markers were found in the families with Charcot-Marie-Tooth syndrome.

There was no evidence for linkage between HLA on the one hand and Friedreich ataxia or hereditary spastic paraplegia on the other.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

HA :

Hereditary ataxias

HLA :

Major histocompatibility system

CA :

Cerebellar ataxia

FA :

Friedreich ataxia

HSP :

Hereditary spastic paraplegia

CMT :

Charcot-Marie-Tooth syndrome

MS :

Multiple sclerosis

Hp :

Haptoglobin

Gc :

Group-specific component

PGM :

Phosphoglucomutase, locus 1

SP (AcP) :

Acid phosphatase

AK :

Adenylatekinase

PGD :

6-phosphogluconatedehydrogenase

ADA :

Adenosinedeaminase

GPT :

Glutamate pyruvat transaminase

GT :

Galaktose-1-phosphat uridylyltransferase

EsP :

Carboxylesterase D

GLO :

Glyoxylase I

References

  • Bugiani, O., Bogaert, L. van: Sur la transformation dans le temps des phenotypes abiotrophiques. Psychiat. Neurol. Neurochir. 70, 281–304 (1967)

    Google Scholar 

  • Currier, R. D., Glover, G., Jackson, J. F., Tipton, A. C.: Spinocerebellar ataxia: Study of a large kindred. Neurology (Minneap.) 22, 1040–1043 (1972)

    Google Scholar 

  • Friedreich, N.: Über Ataxia mit besonderer Berücksichtigung der hereditären Formen. Virchows Arch. Pathol. Anat. 68, 145–245 (1876)

    Google Scholar 

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

    Google Scholar 

  • Jackson, J. F., Whittington, J. E., Currier, R. D., Terasaki, P. I., Morton, N. E., Keats, B. J. B.: Genetic linkage and spinocerebellar ataxia. In: Advances in Neurology 21 (R. A. P. Kark, R. N. Rosenberg, L. J. Schut, eds.), pp. 315–318. New York: Raven Press 1978

    Google Scholar 

  • Kissmeyer-Nielsen, F., Kjerbye, K. E.: In: Histocompatibility testing, p. 381. Copenhagen: Munksgaard 1967

    Google Scholar 

  • Lamm, L. U., Thorsen, I., Petersen, G. B., Jørgensen, J., Henningsen, K., Bech, B., Kissmeyer-Nielsen, F.: Data on the HL-A linkage group. Ann. Hum. Genet. 38, 383 (1975)

    Google Scholar 

  • Marie, P.: Clinique des maladies nerveuses. Sur l'heredo-ataxie cerebelleuse. Sem. Med. 13, 444–447 (1893)

    Google Scholar 

  • Morton, N. W.: The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type. Am. J. Hum. Genet. 8, 83–96 (1956)

    Google Scholar 

  • Møller, E., Hindfelt, B., Olsson, J.: HLA-determination in families with hereditary ataxia. Tissue Antigens 12, 357–366 (1978)

    Google Scholar 

  • Nino, H. E., Noreen, H. J., Yunis, J., Resch, J. A., Dubey, D. P.: A family with hereditary ataxia: Results of HLA typing (abstract). Neurology (Minneap.) 28, 353 (1978)

    Google Scholar 

  • Olaisen, B., Gedde-Dahl, T., Thorsby, E.: Localization of the human GLO gene locus. Hum. Genet. 32, 301–304 (1976)

    Google Scholar 

  • Ott, J.: Estimation of the recombination fraction in human pedigrees. Efficient compensation of the likelihood for human linkage studies. Am. J. Hum. Genet. 26, 588–597 (1974)

    Google Scholar 

  • Pedersen, L., Platz, P., Raun, N. E.: Hereditary ataxia, immunological in vitro parameters and HLA. (In press, 1980)

  • Pedersen, L.: Hereditary ataxia in a large Danish pedigree. (In press, 1980)

  • Petersen, G. Bruun, Sørensen, I., Buskjaer, L., Lamm, L. U.: Genetic studies of complement C4. Hum. Genet. (In press, 1980)

  • Pratt, R. T. C.: The genetics of neurological disorders. London: Oxford University Press 1967

    Google Scholar 

  • Rosenberg, L. E., Kidd, K. K.: HLA and disease susceptibility: A primer. New Engl. J. Med. 297, 1060–1062 (1977)

    Google Scholar 

  • Ryder, L. P., Andersen, E., Svejgaard, A.: HLA and disease registry. Third report. Copenhagen: Munksgaard 1979

    Google Scholar 

  • Schut, J. W.: Hereditary ataxia. Clinical study through six generations. Arch. Neurol. (Chicago) 63, 535–568 (1950)

    Google Scholar 

  • Skre, H.: Genetic and clinical aspects of Charcot-Marie-Tooth's disease. Clin. Genet. 6, 98–118 (1974)

    Google Scholar 

  • Svejgaard, A., Jersild, C., Staub Nielsen, L., Bodmer, W. F.: HL-A antigens and disease. Statistical and genetical considerations. Tissue Antigens 4, 95–105 (1974)

    Google Scholar 

  • Wastiaux, J. P., Lamoureux, G., Bouchard, J. P., Durivage, A., Barbeau, C., Barbeau, A.: HLA and complement typing in olivo-ponto-cerebellar atrophy. J. Ca. Sci. Neur. 5, 75–81 (1978)

    Google Scholar 

  • Weitkamp, L. R., Rood, J. J. van, Thorsby, E., Bias, W.: The relation of parental sex and age to recombination in the HL-A system. Hum. Hered. 23, 197–205 (1973)

    Google Scholar 

  • Weitkamp, L. R., May, A. G., Johnston, E.: The linkage relationships of HL-A with other genetic marker systems. Hum. Hered. 25, 337–345 (1975)

    Google Scholar 

  • Yakura, H., Wakisaka, A., Fujimoto, S., Itakura, K.: Hereditary ataxia and HL-A genotypes. New Engl. J. Med. 291, 154–155 (1974)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurological Department, Municipal Hospital, Øster Farimagsgade 5, DK-1399, Copehagen

    Lene Pedersen

  2. Tissue Typing Laboratory of the Blood Grouping Department, State University Hospital, Copenhagen

    P. Platz & L. P. Ryder

  3. Tissue Typing Laboratory, University Hospital, Århus

    L. U. Lamm

  4. Institute of Forensic Medicine, Department of Serology, University of Copenhagen, Denmark

    J. Dissing

Authors
  1. Lene Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Platz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. P. Ryder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. U. Lamm
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Dissing
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was aided by grants from Warwara Larsen's Foundation, the Danish Multiple Sclerosis Society and the Medical Research Council

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pedersen, L., Platz, P., Ryder, L.P. et al. A linkage study of hereditary ataxias and related disorders. Hum Genet 54, 371–383 (1980). https://doi.org/10.1007/BF00291585

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00291585

Keywords

Search

Navigation