Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Jan;56(1):188–192.

Autosomal dominant familial spastic paraplegia: tight linkage to chromosome 15q.

J K Fink 1, C T Wu 1, S M Jones 1, G B Sharp 1, B M Lange 1, A Lesicki 1, T Reinglass 1, T Varvil 1, B Otterud 1, M Leppert 1
PMCID: PMC1801321  PMID: 7825577

Abstract

Autosomal dominant, uncomplicated familial spastic paraplegia (FSP) is a genetically heterogeneous disorder characterized by insidiously progressive lower-extremity spasticity. Recently, a locus on chromosome 14q was shown to be tightly linked with the disorder in one of three families. We performed linkage analysis in a kindred with autosomal dominant uncomplicated FSP. After excluding the chromosome 14q locus, we observed tight linkage of the disorder to a group of markers on chromosome 15q (maximum two-point lod score 9.70; theta = .05). Our results clearly establish the existence of a locus for autosomal dominant FSP in the centromeric region of chromosome 15q. Comparing clinical and genetic features in FSP families linked to chromosome 14q with those linked to chromosome 15q may provide insight into the pathophysiology of this disorder.

Full text

PDF
188

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Behan W. M., Maia M. Strümpell's familial spastic paraplegia: genetics and neuropathology. J Neurol Neurosurg Psychiatry. 1974 Jan;37(1):8–20. doi: 10.1136/jnnp.37.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boustany R. M., Fleischnick E., Alper C. A., Marazita M. L., Spence M. A., Martin J. B., Kolodny E. H. The autosomal dominant form of "pure" familial spastic paraplegia: clinical findings and linkage analysis of a large pedigree. Neurology. 1987 Jun;37(6):910–915. doi: 10.1212/wnl.37.6.910. [DOI] [PubMed] [Google Scholar]
  4. Cartlidge N. E., Bone G. Sphincter involvement in hereditary spastic paraplegia. Neurology. 1973 Nov;23(11):1160–1163. doi: 10.1212/wnl.23.11.1160. [DOI] [PubMed] [Google Scholar]
  5. Chamberlain S., Farrall M., Shaw J., Wilkes D., Carvajal J., Hillerman R., Doudney K., Harding A. E., Williamson R., Sirugo G. Genetic recombination events which position the Friedreich ataxia locus proximal to the D9S15/D9S5 linkage group on chromosome 9q. Am J Hum Genet. 1993 Jan;52(1):99–109. [PMC free article] [PubMed] [Google Scholar]
  6. Dürr A., Brice A., Serdaru M., Rancurel G., Derouesné C., Lyon-Caen O., Agid Y., Fontaine B. The phenotype of "pure" autosomal dominant spastic paraplegia. Neurology. 1994 Jul;44(7):1274–1277. doi: 10.1212/wnl.44.7.1274. [DOI] [PubMed] [Google Scholar]
  7. Harding A. E. Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry. 1981 Oct;44(10):871–883. doi: 10.1136/jnnp.44.10.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hazan J., Lamy C., Melki J., Munnich A., de Recondo J., Weissenbach J. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet. 1993 Oct;5(2):163–167. doi: 10.1038/ng1093-163. [DOI] [PubMed] [Google Scholar]
  9. Holmes G. L., Shaywitz B. A. Strumpell's pure familial spastic paraplegia: case study and review of the literature. J Neurol Neurosurg Psychiatry. 1977 Oct;40(10):1003–1008. doi: 10.1136/jnnp.40.10.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kenwrick S., Ionasescu V., Ionasescu G., Searby C., King A., Dubowitz M., Davies K. E. Linkage studies of X-linked recessive spastic paraplegia using DNA probes. Hum Genet. 1986 Jul;73(3):264–266. doi: 10.1007/BF00401241. [DOI] [PubMed] [Google Scholar]
  11. Keppen L. D., Leppert M. F., O'Connell P., Nakamura Y., Stauffer D., Lathrop M., Lalouel J. M., White R. Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet. 1987 Nov;41(5):933–943. [PMC free article] [PubMed] [Google Scholar]
  12. 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. 1985 May;37(3):482–498. [PMC free article] [PubMed] [Google Scholar]
  13. Lupski J. R., de Oca-Luna R. M., Slaugenhaupt S., Pentao L., Guzzetta V., Trask B. J., Saucedo-Cardenas O., Barker D. F., Killian J. M., Garcia C. A. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 1991 Jul 26;66(2):219–232. doi: 10.1016/0092-8674(91)90613-4. [DOI] [PubMed] [Google Scholar]
  14. Opjordsmoen S., Nyberg-Hansen R. Hereditary spastic paraplegia with neurogenic bladder disturbances and syndactylia. Acta Neurol Scand. 1980 Jan;61(1):35–41. doi: 10.1111/j.1600-0404.1980.tb02993.x. [DOI] [PubMed] [Google Scholar]
  15. Polo J. M., Calleja J., Combarros O., Berciano J. Hereditary "pure" spastic paraplegia: a study of nine families. J Neurol Neurosurg Psychiatry. 1993 Feb;56(2):175–181. doi: 10.1136/jnnp.56.2.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. ROE P. F. HEREDITARY SPASTIC PARAPLEGIA. J Neurol Neurosurg Psychiatry. 1963 Dec;26:516–519. doi: 10.1136/jnnp.26.6.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ranum L. P., Duvick L. A., Rich S. S., Schut L. J., Litt M., Orr H. T. 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. 1991 Jul;49(1):31–41. [PMC free article] [PubMed] [Google Scholar]
  18. Roa B. B., Garcia C. A., Suter U., Kulpa D. A., Wise C. A., Mueller J., Welcher A. A., Snipes G. J., Shooter E. M., Patel P. I. Charcot-Marie-Tooth disease type 1A. Association with a spontaneous point mutation in the PMP22 gene. N Engl J Med. 1993 Jul 8;329(2):96–101. doi: 10.1056/NEJM199307083290205. [DOI] [PubMed] [Google Scholar]
  19. SCHWARZ G. A., LIU C. N. Hereditary (familial) spastic paraplegia; further clinical and pathologic observations. AMA Arch Neurol Psychiatry. 1956 Feb;75(2):144–162. doi: 10.1001/archneurpsyc.1956.02330200038005. [DOI] [PubMed] [Google Scholar]
  20. Scheltens P., Bruyn R. P., Hazenberg G. J. A Dutch family with autosomal dominant pure spastic paraparesis (Strümpell's disease). Acta Neurol Scand. 1990 Sep;82(3):169–173. doi: 10.1111/j.1600-0404.1990.tb04484.x. [DOI] [PubMed] [Google Scholar]
  21. Skre H. Hereditary spastic paraplegia in Western Norway. Clin Genet. 1974;6(3):165–183. doi: 10.1111/j.1399-0004.1974.tb00647.x. [DOI] [PubMed] [Google Scholar]
  22. Takiyama Y., Nishizawa M., Tanaka H., Kawashima S., Sakamoto H., Karube Y., Shimazaki H., Soutome M., Endo K., Ohta S. The gene for Machado-Joseph disease maps to human chromosome 14q. Nat Genet. 1993 Jul;4(3):300–304. doi: 10.1038/ng0793-300. [DOI] [PubMed] [Google Scholar]
  23. Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES