Abstract
Autosomal dominant familial spastic paraplegia (FSP) is a degenerative disorder of unknown aetiology characterized by a progressive spasticity of the legs. Three families with autosomal dominant FSP of early onset were analysed in linkage studies using highly polymorphic microsatellite markers. Close linkage to a group of markers on chromosome 14q (maximum multipoint lodscore z=10) was observed in one family. This chromosome 14q candidate region was entirely excluded in the two other families, providing evidence of genetic heterogeneity within a homogeneous clinical form of FSP.
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References
Seeligmüller, A. Sklerose der seitenstrange des Rückenmarks bei 4 Kindern derselben Familie. Dtsch. med. Wochenschr. 2, 185–186 (1876).
Strümpell, A. Beiträge zur Pathologie des Rückenmarks. Arch. Psychiatr. Nervenkr. 10, 676–717 (1880).
Sutherland, J.M. Familial spastic paraplegia, in Handbook of Clinical Neurology 22 (eds Vinken, P.J. & Bruyn, G.W.) 421–431 (North Holland Publishing Company, Amsterdam, 1975).
Holmes, G.L. & Shaywitz, B.A. Strümpell's pure familial spastic paraplegia: Case study and review of the literature. J. Neurol. Neurosurg. Psychiatry. 40, 1003–1008 (1977).
McKusick, V.A. . in Mendelian Inheritance in Man (9th edn) 864 (The Johns Hopkins University Press, Baltimore and London, 1990).
Keppen, L.D. et al. Biological heterogeneity in X-linked spastic paraplegia. Am. J. hum. Genet. 41, 933–943 (1987).
Harding, A.E. Hereditary “pure” spastic paraplegia: a clinical and genetic study of 22 families. J. Neurol. Neurosurg. Psychiatry 44, 871–883 (1981).
Harding, A.E. Classification of the hereditary ataxias and paraplegias. Lancet 1, 1151–1155 (1983).
Schady, W. & Sheard, A. A quantitative study of sensory function in hereditary spastic paraplegia. Brain 113, 709–720 (1990).
Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992).
Boustany, R-M.N. et al. The autosomal dominant form of “pure” familial spastic paraplegia: Clinical findings and linkage analysis of a large pedigree. Neurology 37, 910–915 (1987).
Claudio, J.O. et al. Genetic linkage mapping of hereditary spastic paraplegia. Am. J. hum Genet. 51, A361 (1992).
van Deutekom, J., van den Boorn, N., Padberg, G.W. & Frants, R.R. Linkage analysis in a Dutch family with “pure” familial spastic paraplegia (FSP). Am. J. hum. Genet. 52, A375 (1992).
Church, G.M. & Kieffer-Higgins, S. Multiplex DNA sequencing. Science 240, 185–188 (1988).
Hazan, J., Dubay, C., Pankowiak, M.-P., Becuwe, N. & Weissenbach, J. A genetic linkage map of human chromosome 20 composed entirely of microsatellite markers. Genomics 12, 83–189 (1992).
Vignal, A. et al. A non-radioactive multiplex procedure for genotyping of microsatellite markers, in Methods in Molecular Genetics 1, (ed. Adolph, K.W., in the press, 1993).
Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Multilocus linkage analysis in humans: Detection of linkage and estimation of recombination. Am. J. hum. Genet. 37, 482–498 (1985).
Vance, J.M. Hereditary motor and sensory neuropathies. J. med. Genet. 28, 1–5 (1991).
Kenwrick, S. et al. Linkage studies of X-linked recessive spastic paraplegia using DNA probes. Hum. Genet. 73, 264–266 (1986).
Suthers, G.K. & Davies, K.E. Phenotypic heterogeneity and the single gene. Am. J. hum. Genet. 50, 887–891 (1992).
Polo, J.M., Calleja, J., Combarros, O. & Berciano, J. Hereditary “pure” spastic paraplegia: a study of nine families. J. Neurol. Neurosurg. Psychiatry 56, 175–181 (1993).
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Hazan, J., Lamy, C., Melki, J. et al. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet 5, 163–167 (1993). https://doi.org/10.1038/ng1093-163
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DOI: https://doi.org/10.1038/ng1093-163
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