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. 1990 Apr;46(4):652–660.

Cosegregation of elastin-associated microfibrillar abnormalities with the Marfan phenotype in families.

M Godfrey 1, V Menashe 1, R G Weleber 1, R D Koler 1, R H Bigley 1, E Lovrien 1, J Zonana 1, D W Hollister 1
PMCID: PMC1683653  PMID: 2180284

Abstract

The Marfan syndrome is a serious heritable connective-tissue disorder characterized primarily by ocular, cardiovascular, and musculoskeletal abnormalities but also involving multiple other tissues and organs of the body. Inherited as an autosomal dominant disorder, the etiology and pathogenesis of the Marfan syndrome are presently unknown. We have documented consistent apparent deficient content of elastin-associated microfibrillar fibers by indirect immunofluorescent (IF) studies of Marfan skin, as well as deficient accumulation of related fibrous materials in cultures of Marfan fibroblasts as compared with normal controls and patients with other heritable disorders of connective tissue. These data have suggested that abnormalities in the microfibrillar component of elastic-fiber systems may have a role in the etiology and pathogenesis of the Marfan syndrome. In the present study, we have analyzed the IF staining patterns of skin and fibroblast cultures from Marfan syndrome patients and normal first-degree relatives in nine Marfan kindreds. Three of these families had at least one affected individual in each of 2 generations, permitting intergenerational comparison of IF patterns. Six kindreds had one or more affected individuals in a single generation, making comparisons between siblings and/or parent-child possible. In all cases, IF abnormalities cosegregated with the Marfan phenotype and all nonaffected family members were normal. Within family groups containing more than one affected individual, the IF staining patterns were similar between affected patients. These data provide further confirmation of consistent and relatively specific deficiency of microfibrillar fibers in Marfan syndrome.

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Selected References

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

  1. 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]
  2. 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]
  3. 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]
  4. Burgio R. G., Martini A., Cetta G., Zanaboni G., Vitellaro L., Danesino C. Asymmetric Marfan syndrome. Am J Med Genet. 1988 Aug;30(4):905–909. doi: 10.1002/ajmg.1320300405. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Cleary E. G., Gibson M. A. Elastin-associated microfibrils and microfibrillar proteins. Int Rev Connect Tissue Res. 1983;10:97–209. doi: 10.1016/b978-0-12-363710-9.50009-5. [DOI] [PubMed] [Google Scholar]
  7. Colombatti A., Bonaldo P., Volpin D., Bressan G. M. The elastin associated glycoprotein gp115. Synthesis and secretion by chick cells in culture. J Biol Chem. 1988 Nov 25;263(33):17534–17540. [PubMed] [Google Scholar]
  8. Cotta-Pereira G., Guerra Rodrigo F., Bittencourt-Sampaio S. Oxytalan, elaunin, and elastic fibers in the human skin. J Invest Dermatol. 1976 Mar;66(3):143–148. doi: 10.1111/1523-1747.ep12481882. [DOI] [PubMed] [Google Scholar]
  9. 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]
  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. Gibson M. A., Hughes J. L., Fanning J. C., Cleary E. G. The major antigen of elastin-associated microfibrils is a 31-kDa glycoprotein. J Biol Chem. 1986 Aug 25;261(24):11429–11436. [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. LOW F. N. Microfibrils: fine filamentous components of the tissue space. Anat Rec. 1962 Feb;142:131–137. doi: 10.1002/ar.1091420205. [DOI] [PubMed] [Google Scholar]
  14. Lamberg S. I., Dorfman A. Synthesis and degradation of hyaluronic acid in the cultured fibroblasts of Marfan's disease. J Clin Invest. 1973 Oct;52(10):2428–2433. doi: 10.1172/JCI107433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maumenee I. H. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc. 1981;79:684–733. [PMC free article] [PubMed] [Google Scholar]
  16. Mecham R. P., Hinek A., Cleary E. G., Kucich U., Lee S. J., Rosenbloom J. Development of immunoreagents to ciliary zonules that react with protein components of elastic fiber microfibrils and with elastin-producing cells. Biochem Biophys Res Commun. 1988 Mar 15;151(2):822–826. doi: 10.1016/s0006-291x(88)80355-3. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Perejda A. J., Abraham P. A., Carnes W. H., Coulson W. F., Uitto J. Marfan's syndrome: structural, biochemical, and mechanical studies of the aortic media. J Lab Clin Med. 1985 Oct;106(4):376–383. [PubMed] [Google Scholar]
  19. Pyeritz R. E., Fishman E. K., Bernhardt B. A., Siegelman S. S. Dural ectasia is a common feature of the Marfan syndrome. Am J Hum Genet. 1988 Nov;43(5):726–732. [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Raviola G. The fine structure of the ciliary zonule and ciliary epithelium. With special regard to the organization and insertion of the zonular fibrils. Invest Ophthalmol. 1971 Nov;10(11):851–869. [PubMed] [Google Scholar]
  22. Rosenbloom J. Elastin: relation of protein and gene structure to disease. Lab Invest. 1984 Dec;51(6):605–623. [PubMed] [Google Scholar]
  23. Sakai L. Y., Keene D. R., Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986 Dec;103(6 Pt 1):2499–2509. doi: 10.1083/jcb.103.6.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saruk M., Eisenstein R. Aortic lesion in Marfan syndrome: the ultrastructure of cystic medial degeneration. Arch Pathol Lab Med. 1977 Feb;101(2):74–77. [PubMed] [Google Scholar]
  25. Serafini-Fracassini A., Ventrella G., Field M. J., Hinnie J., Onyezili N. I., Griffiths R. Characterization of a structural glycoprotein from bovine ligamentum nuchae exhibiting dual amine oxidase activity. Biochemistry. 1981 Sep 15;20(19):5424–5429. doi: 10.1021/bi00522a011. [DOI] [PubMed] [Google Scholar]
  26. Streeten B. W., Swann D. A., Licari P. A., Robinson M. R., Gibson S. A., Marsh N. J., Vergnes J. P., Freeman I. L. The protein composition of the ocular zonules. Invest Ophthalmol Vis Sci. 1983 Jan;24(1):119–123. [PubMed] [Google Scholar]
  27. Takebayashi S., Taguchi T., Kawamura K., Sakata N. "Osmiophilic elastolysis" of peripheral organ arteries in patients with Marfan's syndrome. Acta Pathol Jpn. 1988 Nov;38(11):1433–1443. doi: 10.1111/j.1440-1827.1988.tb01085.x. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Tsuji T. Marfan syndrome: demonstration of abnormal elastic fibers in skin. J Cutan Pathol. 1986 Apr;13(2):144–153. doi: 10.1111/j.1600-0560.1986.tb01515.x. [DOI] [PubMed] [Google Scholar]

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