Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity (original) (raw)

. 1991 Oct;49(4):764–772.

Abstract

Tuberous sclerosis (TSC) is an autosomal dominant disorder with both neurological and cutaneous manifestations often resulting in significant disability. Although it has been studied clinically and biochemically for many years, the underlying pathophysiology remains unknown. Genetic linkage analysis provides an alternative strategy for understanding the genetic etiology of this disease. Genetic linkage of a gene for TSC to loci in 9q32-9q34 has been reported but has not been a universal finding, since absence of linkage to 9q loci, as well as linkage to loci on 11q, have also been reported. We present here data on 22 families (21 previously unreported) segregating TSC. Our results strongly support a TSC locus in the 9q32-34 region for approximately one-third of families and provide significant evidence for genetic heterogeneity. Application of newly described highly polymorphic dinucleotide repeat marker loci in TSC greatly enhanced the informativeness of our pedigrees and was vital for detecting the heterogeneity. No clear evidence of linkage to chromosome 11q22 markers was found, suggesting that a still unidentified TSC locus elsewhere in the genome may account for the majority of TSC families.

764

Selected References

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

  1. Anderson M. A., Gusella J. F. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984 Nov;20(11):856–858. doi: 10.1007/BF02619631. [DOI] [PubMed] [Google Scholar]
  2. Connor J. M., Pirrit L. A., Yates J. R., Fryer A. E., Ferguson-Smith M. A. Linkage of the tuberous sclerosis locus to a DNA polymorphism detected by v-abl. J Med Genet. 1987 Sep;24(9):544–546. doi: 10.1136/jmg.24.9.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  4. Fryer A. E., Chalmers A., Connor J. M., Fraser I., Povey S., Yates A. D., Yates J. R., Osborne J. P. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet. 1987 Mar 21;1(8534):659–661. doi: 10.1016/s0140-6736(87)90416-8. [DOI] [PubMed] [Google Scholar]
  5. Haines J. L., Amos J., Attwood J., Bech-Hansen N. T., Burley M., Conneally P. M., Connor J. M., Fahsold R., Flodman P., Fryer A. Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset. Ann N Y Acad Sci. 1991;615:256–264. doi: 10.1111/j.1749-6632.1991.tb37767.x. [DOI] [PubMed] [Google Scholar]
  6. Hunt A., Dennis J. Psychiatric disorder among children with tuberous sclerosis. Dev Med Child Neurol. 1987 Apr;29(2):190–198. doi: 10.1111/j.1469-8749.1987.tb02135.x. [DOI] [PubMed] [Google Scholar]
  7. Janssen L. A., Povey S., Attwood J., Sandkuyl L. A., Lindhout D., Flodman P., Smith M., Sampson J. R., Haines J. L., Merkens E. C. A comparative study on genetic heterogeneity in tuberous sclerosis: evidence for one gene on 9q34 and a second gene on 11q22-23. Ann N Y Acad Sci. 1991;615:306–315. doi: 10.1111/j.1749-6632.1991.tb37772.x. [DOI] [PubMed] [Google Scholar]
  8. Janssen L. A., Sandkuyl L. A., Merkens E. C., Maat-Kievit J. A., Sampson J. R., Fleury P., Hennekam R. C., Grosveld G. C., Lindhout D., Halley D. J. Genetic heterogeneity in tuberous sclerosis. Genomics. 1990 Oct;8(2):237–242. doi: 10.1016/0888-7543(90)90277-2. [DOI] [PubMed] [Google Scholar]
  9. Julier C., Nakamura Y., Lathrop M., O'Connell P., Leppert M., Litt M., Mohandas T., Lalouel J. M., White R. A detailed genetic map of the long arm of chromosome 11. Genomics. 1990 Jul;7(3):335–345. doi: 10.1016/0888-7543(90)90167-s. [DOI] [PubMed] [Google Scholar]
  10. Kandt R. S., Pericak-Vance M. A., Hung W. Y., Gardner R. J., Nellist M., Phillips K., Warner K., Speer M. C., Crossen P. E., Laing N. G. Absence of linkage of ABO blood group locus to familial tuberous sclerosis. Exp Neurol. 1989 Jun;104(3):223–228. doi: 10.1016/0014-4886(89)90033-2. [DOI] [PubMed] [Google Scholar]
  11. Kwiatkowski D. J. Dinucleotide repeat polymorphism at the ABL locus (9q34). Nucleic Acids Res. 1991 Feb 25;19(4):967–967. [PMC free article] [PubMed] [Google Scholar]
  12. Kwiatkowski D. J., Nygaard T. G., Schuback D. E., Perman S., Trugman J. M., Bressman S. B., Burke R. E., Brin M. F., Ozelius L., Breakefield X. O. Identification of a highly polymorphic microsatellite VNTR within the argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as the cause of dopa-responsive dystonia in a large kindred. Am J Hum Genet. 1991 Jan;48(1):121–128. [PMC free article] [PubMed] [Google Scholar]
  13. Kwiatkowski D. J., Perman S. Dinucleotide repeat polymorphism at the GSN locus (9q32-34). Nucleic Acids Res. 1991 Feb 25;19(4):967–967. [PMC free article] [PubMed] [Google Scholar]
  14. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Northrup H., Beaudet A. L., O'Brien W. E., Herman G. E., Lewis R. A., Pollack M. S. Linkage of tuberous sclerosis to ABO blood group. Lancet. 1987 Oct 3;2(8562):804–805. doi: 10.1016/s0140-6736(87)92543-8. [DOI] [PubMed] [Google Scholar]
  16. Ploughman L. M., Boehnke M. Estimating the power of a proposed linkage study for a complex genetic trait. Am J Hum Genet. 1989 Apr;44(4):543–551. [PMC free article] [PubMed] [Google Scholar]
  17. Povey S., Attwood J., Janssen L. A., Burley M., Smith M., Flodman P., Morton N. E., Edwards J. H., Sampson J. R., Yates J. R. An attempt to map two genes for tuberous sclerosis using novel two-point methods. Ann N Y Acad Sci. 1991;615:298–305. doi: 10.1111/j.1749-6632.1991.tb37771.x. [DOI] [PubMed] [Google Scholar]
  18. Sampson J. R., Scahill S. J., Stephenson J. B., Mann L., Connor J. M. Genetic aspects of tuberous sclerosis in the west of Scotland. J Med Genet. 1989 Jan;26(1):28–31. doi: 10.1136/jmg.26.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sampson J. R., Yates J. R., Pirrit L. A., Fleury P., Winship I., Beighton P., Connor J. M. Evidence for genetic heterogeneity in tuberous sclerosis. J Med Genet. 1989 Aug;26(8):511–516. doi: 10.1136/jmg.26.8.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith M., Smalley S., Cantor R., Pandolfo M., Gomez M. I., Baumann R., Flodman P., Yoshiyama K., Nakamura Y., Julier C. Mapping of a gene determining tuberous sclerosis to human chromosome 11q14-11q23. Genomics. 1990 Jan;6(1):105–114. doi: 10.1016/0888-7543(90)90454-3. [DOI] [PubMed] [Google Scholar]
  21. Trofatter J. A., Haines J. L., Conneally P. M. LIPIN: an interactive data entry and management program for LIPED. Am J Hum Genet. 1986 Jul;39(1):147–148. [PMC free article] [PubMed] [Google Scholar]
  22. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  23. Wiederholt W. C., Gomez M. R., Kurland L. T. Incidence and prevalence of tuberous sclerosis in Rochester, Minnesota, 1950 through 1982. Neurology. 1985 Apr;35(4):600–603. doi: 10.1212/wnl.35.4.600. [DOI] [PubMed] [Google Scholar]