Marfan syndrome : defective synthesis, secretion, and extracellular matrix formation of fibrillin by cultured dermal fibroblasts

• Published in: The Journal of clinical investigation Vol. 89; no. 1; pp. 79 - 86
• Main Authors: MCGOOKEY MILEWICZ, D, PYERITZ, R. E, CRAWFORD, E. S, BYERS, P. H
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 1992
• Subjects: Adolescent; Adult; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Female; fibrillin; Fibrillins; Fibroblasts - metabolism; Fibroblasts - pathology; Genetic Variation; Humans; Infant; Male; Marfan Syndrome - metabolism; Medical sciences; Microfilament Proteins - metabolism; Microfilament Proteins - secretion; Mutation; Phenotype; Protein Processing, Post-Translational; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - cytology; Skin - metabolism; Skin - pathology; Human; Exploration; Extracellular matrix; Marfan syndrome; Microfibril
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci115589

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.