Abstract
Pure hereditary spastic paraparesis (HSP) is an upper motor neuron syndrome clinically characterized by slowly progressive weakness and spasticity of the legs. To determine the chromosomal location of the genetic defect, a five-generational Dutch family with autosomal dominant pure HSP was subjected to linkage studies. Analysis was carried out on 48 members spanning three generations, of whom 23 individuals are definitely affected. By screening the genome with a total of 167 microsatellite markers distributed over all autosomes, an exclusion map for HSP was constructed. Depending on the actual size of the human genome, our exclusion map covered between 40% and 65% of its autosomal length. Loci on chromosomes 1, 8, 13, 14, and 18 showed slightly positive lod scores. The areas around these loci were investigated more closely, but no conclusive evidence for, or against, linkage could be obtained.
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References
Boustany RMN, Fleischnik E, Alper CA, Marazita ML, Spence MA, Martin JB, Kolodny EH (1987) The autosomal dominant form of “pure” familial spastic paraplegia:Clinical findings and linkage analysis of a large pedigree. Neurology 37:910–915
Bruyn RPM, Scheltens Ph (1991) Hereditary spastic paraparesis (Strümpell-Lorrain). In: Vinken PJ, Bruyn GW, Klawans HL (eds) Handbook of clinical neurology. Elsevier Science Publishers, Amsterdam, pp 301–318
Bruyn RPM, Van Deutekom JCT, Frants RR, Padberg GW (1993) Hereditary spastic paraparesis: Clinical and genetic data from a large Dutch family. Clin Neurol Neurosurg 95:125–129
Haldane JBS (1919) The combination of linkage values and the calculation of distances between the loci of linked factors. J Genet 8:299–309
Harding AE (1981) Hereditary “pure” spastic paraplegia: a clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry 44:871–883
Heutink P, Mey AGL van der, Sandkuijl LA, Gils APG van, Bardoel A, Breedveld GJ, Vliet M van, Ommen GJB van, Cornelisse CJ, Oostra BA, Weber JL, Devilee P (1992) A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. Hum Mol Genet 1:7–10
Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446
Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from nucleated cells. Nucleic Acids Res 16:1215
Morton NE (1991) Parameters of the human genome. Proc Natl Acad Sci USA 88:7474–7476
Nancarrow DJ, Walker GJ, Weber JL, Walters MK, Palmer JM, Hayward NK (1992) Linkage mapping of melanoma (MLM) using 172 microsatellite markers. Genomics 14:939–947
NIH/CEPH Collaborative Mapping Group (1992) A comprehensive genetic linkage map of the human genome. Science 258:67–86
Renwick JH (1969) Progress in mapping human autosomes. Br Med Bull 25:65–73
Strümpell A (1886) Über eine bestimmte Form der primären combinierten Systemerkrankung des Rückenmarks. Arch Psychiat Nervenker 17:217–238
Weber J, May PE (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44:388–396
Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M (1992) A second-generation linkage map of the human genome. Nature 359:794–801
Wijmenga C, Frants RR, Brouwer OF, Moerer P, Weber JL, Padberg GW (1990) Location of facioscapulohumeral muscular dystrophy gene on chromosome 4. Lancet 336:651–653
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van Deutekom, J.C.T., Bruyn, R.P.M., van den Boom, N. et al. Pure hereditary spastic paraparesis: an exclusion map covering more than 40% of the autosomal genome. Hum Genet 93, 408–414 (1994). https://doi.org/10.1007/BF00201665
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DOI: https://doi.org/10.1007/BF00201665