Marfan Syndrome: Defective Synthesis, Secretion, and Extracellular Matrix Formation of Fibrillin by Cultured Dermal Fibroblasts

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1992 Jan 1

PMID 1729284

Citations 60

Authors

D M Milewicz

R E Pyeritz

E S Crawford

P H Byers

Affiliations

Soon will be listed here.

Abstract

We studied the synthesis, secretion, and aggregation into the extracellular matrix of fibrillin by dermal fibroblasts from 26 probands with the Marfan syndrome. Cells from seven probands synthesized approximately half the normal amount of fibrillin when compared with intrafamilial or unrelated controls. Cells from an additional seven probands synthesized a normal amount of fibrillin but secreted the protein less efficiently than control cells. Cells from a further eight probands synthesized and secreted normal amounts of fibrillin but the protein was poorly incorporated into extracellular matrix. Cells from the remaining four probands were indistinguishable from control cells in their synthesis and processing of fibrillin. Cells from 18 family members of 10 of the probands were also studied. Cells from affected individuals in the same family had the same biochemical defect and those from unaffected family members were indistinguishable from controls. These results indicate that mutations in the gene that encodes fibrillin are responsible for the Marfan syndrome in the majority of individuals (confirming recent immunohistochemical and genetic linkage studies) and that a variety of mutations can produce the phenotype associated with the syndrome.

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References

Godfrey M, Olson S, Burgio R, Martini A, Valli M, Cetta G . Unilateral microfibrillar abnormalities in a case of asymmetric Marfan syndrome. Am J Hum Genet. 1990; 46(4):661-71. PMC: 1683667. View

Bonadio J, Holbrook K, Gelinas R, Jacob J, Byers P . Altered triple helical structure of type I procollagen in lethal perinatal osteogenesis imperfecta. J Biol Chem. 1985; 260(3):1734-42. View

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; 323(14):935-9. DOI: 10.1056/NEJM199010043231402. View

Cleary E, Gibson M . 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. View

Holbrook K, Byers P . Structural abnormalities in the dermal collagen and elastic matrix from the skin of patients with inherited connective tissue disorders. J Invest Dermatol. 1982; 79 Suppl 1:7s-16s. DOI: 10.1111/1523-1747.ep12544609. View

Streeten B, Licari P, MARUCCI A, DOUGHERTY R . Immunohistochemical comparison of ocular zonules and the microfibrils of elastic tissue. Invest Ophthalmol Vis Sci. 1981; 21(1 Pt 1):130-5. View

Pyeritz R, MCKUSICK V . The Marfan syndrome: diagnosis and management. N Engl J Med. 1979; 300(14):772-7. DOI: 10.1056/NEJM197904053001406. View

Appel A, Horwitz A, DORFMAN A . Cell-free synthesis of hyaluronic acid in Marfan syndrome. J Biol Chem. 1979; 254(23):12199-203. View

Lamberg S, DORFMAN A . Synthesis and degradation of hyaluronic acid in the cultured fibroblasts of Marfan's disease. J Clin Invest. 1973; 52(10):2428-33. PMC: 302501. DOI: 10.1172/JCI107433. View

10.

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; 10(11):851-69. View

11.

Matalon R, DORFMAN A . Acid mucopolysaccharides in cultured human fibroblasts. Lancet. 1969; 2(7625):838-41. DOI: 10.1016/s0140-6736(69)92289-2. View

12.

Ross R, Bornstein P . The elastic fiber. I. The separation and partial characterization of its macromolecular components. J Cell Biol. 1969; 40(2):366-81. PMC: 2107618. DOI: 10.1083/jcb.40.2.366. View

13.

Rodrigo F . Oxytalan, elaunin, and elastic fibers in the human skin. J Invest Dermatol. 1976; 66(3):143-8. DOI: 10.1111/1523-1747.ep12481882. View

14.

Murdoch J, Walker B, Halpern B, KUZMA J, MCKUSICK V . Life expectancy and causes of death in the Marfan syndrome. N Engl J Med. 1972; 286(15):804-8. DOI: 10.1056/NEJM197204132861502. View

15.

Dietz H, Cutting G, Pyeritz R, Maslen C, Sakai L, Corson G . Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991; 352(6333):337-9. DOI: 10.1038/352337a0. View

16.

Maslen C, Corson G, Maddox B, Glanville R, Sakai L . Partial sequence of a candidate gene for the Marfan syndrome. Nature. 1991; 352(6333):334-7. DOI: 10.1038/352334a0. View

17.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

18.

Lee B, Godfrey M, Vitale E, Hori H, Mattei M, Sarfarazi M . Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991; 352(6333):330-4. DOI: 10.1038/352330a0. View

19.

Tsipouras P, Sarfarazi M, Devi A, Weiffenbach B, Boxer M . Marfan syndrome is closely linked to a marker on chromosome 15q1.5----q2.1. Proc Natl Acad Sci U S A. 1991; 88(10):4486-8. PMC: 51685. DOI: 10.1073/pnas.88.10.4486. View

20.

Dietz H, Pyeritz R, Hall B, Cadle R, Hamosh A, Schwartz J . The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics. 1991; 9(2):355-61. DOI: 10.1016/0888-7543(91)90264-f. View