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. 1991 Sep;49(3):662–667.

Marfan syndrome: No evidence for heterogeneity in different populations, and more precise mapping of the gene

Katariina Kainulainen, Beat Steinmann, Francis Collins, Harry C Dietz, Clair A Francomano, Anne Child, Michael W Kilpatrick, David J H Brock, Marion Keston, Reed E Pyeritz, Leena Peltonen
PMCID: PMC1683142  PMID: 1882844

Abstract

Marfan syndrome is a dominantly inherited connective tissue disorder with manifestations in the cardiovascular, ocular, and skeletal systems. The diagnosis is hampered by both high variability in the phenotypic expression and late manifestation of symptoms. The cause of Marfan syndrome remains unknown, but our group has recently reported the genetic linkage of Marfan syndrome to a polymorphic marker on chromosome 15. To analyze the possible heterogeneity behind Marfan syndrome, we have performed linkage analyses for four chromosome 15 markers in 17 families from five different populations: Scottish, English, Swiss, American, and Finnish. By combining the linkage data of all the studied families into a LINKMAP analysis we obtained a maximal LOD score of 11.2, which maps the Marfan syndrome locus between D15S25 and D15S45 on the long arm of chromosome 15. The data reveal no evidence for genetic heterogeneity behind Marfan syndrome and provide us with a more precise location of both the Marfan syndrome locus and flanking markers. This information will provide the basis for the DNA diagnostics of Marfan syndrome in the future.

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Selected References

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

  1. Abraham P. A., Perejda A. J., Carnes W. H., Uitto J. Marfan syndrome. Demonstration of abnormal elastin in aorta. J Clin Invest. 1982 Dec;70(6):1245–1252. doi: 10.1172/JCI110723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Appel A., Horwitz A. L., Dorfman A. Cell-free synthesis of hyaluronic acid in Marfan syndrome. J Biol Chem. 1979 Dec 10;254(23):12199–12203. [PubMed] [Google Scholar]
  3. Beighton P., de Paepe A., Danks D., Finidori G., Gedde-Dahl T., Goodman R., Hall J. G., Hollister D. W., Horton W., McKusick V. A. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet. 1988 Mar;29(3):581–594. doi: 10.1002/ajmg.1320290316. [DOI] [PubMed] [Google Scholar]
  4. Blanton S. H., Sarfarazi M., Eiberg H., de Groote J., Farndon P. A., Kilpatrick M. W., Child A. H., Pope F. M., Peltonen L., Francomano C. A. An exclusion map of Marfan syndrome. J Med Genet. 1990 Feb;27(2):73–77. doi: 10.1136/jmg.27.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boucek R. J., Noble N. L., Gunja-Smith Z., Butler W. T. The Marfan syndrome: a deficiency in chemically stable collagen cross-links. N Engl J Med. 1981 Oct 22;305(17):988–991. doi: 10.1056/NEJM198110223051705. [DOI] [PubMed] [Google Scholar]
  6. Brissenden J. E., Page D. C., de Martinville B., Trowsdale J., Botstein D., Francke U. Regional assignments of three polymorphic DNA segments on human chromosome 15. Genet Epidemiol. 1986;3(4):231–239. doi: 10.1002/gepi.1370030404. [DOI] [PubMed] [Google Scholar]
  7. Byers P. H., Siegel R. C., Peterson K. E., Rowe D. W., Holbrook K. A., Smith L. T., Chang Y. H., Fu J. C. Marfan syndrome: abnormal alpha 2 chain in type I collagen. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7745–7749. doi: 10.1073/pnas.78.12.7745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dalgleish R., Hawkins J. R., Keston M. Exclusion of the alpha 2(I) and alpha 1(III) collagen genes as the mutant loci in a Marfan syndrome family. J Med Genet. 1987 Mar;24(3):148–151. doi: 10.1136/jmg.24.3.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dietz H. C., Pyeritz R. E., Hall B. D., Cadle R. G., Hamosh A., Schwartz J., Meyers D. A., Francomano C. A. The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics. 1991 Feb;9(2):355–361. doi: 10.1016/0888-7543(91)90264-f. [DOI] [PubMed] [Google Scholar]
  10. Francomano C. A., Streeten E. A., Meyers D. A., Pyeritz R. E. Marfan syndrome: exclusion of genetic linkage to three major collagen genes. Am J Med Genet. 1988 Feb;29(2):457–462. doi: 10.1002/ajmg.1320290233. [DOI] [PubMed] [Google Scholar]
  11. Godfrey M., Menashe V., Weleber R. G., Koler R. D., Bigley R. H., Lovrien E., Zonana J., Hollister D. W. Cosegregation of elastin-associated microfibrillar abnormalities with the Marfan phenotype in families. Am J Hum Genet. 1990 Apr;46(4):652–660. [PMC free article] [PubMed] [Google Scholar]
  12. Godfrey M., Olson S., Burgio R. G., Martini A., Valli M., Cetta G., Hori H., Hollister D. W. Unilateral microfibrillar abnormalities in a case of asymmetric Marfan syndrome. Am J Hum Genet. 1990 Apr;46(4):661–671. [PMC free article] [PubMed] [Google Scholar]
  13. Hollister D. W., Godfrey M., Sakai L. Y., Pyeritz R. E. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med. 1990 Jul 19;323(3):152–159. doi: 10.1056/NEJM199007193230303. [DOI] [PubMed] [Google Scholar]
  14. Kainulainen K., Pulkkinen L., Savolainen A., Kaitila I., Peltonen L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990 Oct 4;323(14):935–939. doi: 10.1056/NEJM199010043231402. [DOI] [PubMed] [Google Scholar]
  15. Kainulainen K., Savolainen A., Palotie A., Kaitila I., Rosenbloom J., Peltonen L. Marfan syndrome: exclusion of genetic linkage to five genes coding for connective tissue components in the long arm of chromosome 2. Hum Genet. 1990 Feb;84(3):233–236. doi: 10.1007/BF00200565. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. MORTON N. E. The detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type. Am J Hum Genet. 1956 Jun;8(2):80–96. [PMC free article] [PubMed] [Google Scholar]
  18. Nakamura Y., Lathrop M., O'Connell P., Leppert M., Lalouel J. M., White R. A mapped set of DNA markers for human chromosome 15. Genomics. 1988 Nov;3(4):342–346. doi: 10.1016/0888-7543(88)90125-5. [DOI] [PubMed] [Google Scholar]
  19. Ogilvie D. J., Wordsworth B. P., Priestley L. M., Dalgleish R., Schmidtke J., Zoll B., Sykes B. C. Segregation of all four major fibrillar collagen genes in the Marfan syndrome. Am J Hum Genet. 1987 Dec;41(6):1071–1082. [PMC free article] [PubMed] [Google Scholar]
  20. Pulkkinen L., Kainulainen K., Krusius T., Mäkinen P., Schollin J., Gustavsson K. H., Peltonen L. Deficient expression of the gene coding for decorin in a lethal form of Marfan syndrome. J Biol Chem. 1990 Oct 15;265(29):17780–17785. [PubMed] [Google Scholar]
  21. Pyeritz R. E., McKusick V. A. The Marfan syndrome: diagnosis and management. N Engl J Med. 1979 Apr 5;300(14):772–777. doi: 10.1056/NEJM197904053001406. [DOI] [PubMed] [Google Scholar]
  22. Scheck M., Siegel R. C., Parker J., Chang Y. H., Fu J. C. Aortic aneurysm in Marfan's syndrome: changes in the ultrastructure and composition of collagen. J Anat. 1979 Oct;129(Pt 3):645–657. [PMC free article] [PubMed] [Google Scholar]
  23. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  24. Tsipouras P., Børresen A. L., Bamforth S., Harper P. S., Berg K. Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene. Clin Genet. 1986 Nov;30(5):428–432. [PubMed] [Google Scholar]
  25. Vandenplas S., Wiid I., Grobler-Rabie A., Brebner K., Ricketts M., Wållis G., Bester A., Boyd C., Måthew C. Blot hybridisation analysis of genomic DNA. J Med Genet. 1984 Jun;21(3):164–172. doi: 10.1136/jmg.21.3.164. [DOI] [PMC free article] [PubMed] [Google Scholar]

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