Abnormal secretion or extracellular matrix incorporation of fibrillin by dermal fibroblasts from patients with thoracic aortic aneurysms
- Univ. of Texas Medical School, Houston, TX (United States)
Abnormal synthesis, secretion, and extracellular matrix incorporation of fibrillin is observed in the majority of fibroblast cell strains obtained from individuals with the Marfan syndrome (>85%). These fibrillin protein abnormalities are due to mutations in the FBN1 gene. We have screened fibroblast cell strains from patients with thoracic aortic aneurysms (TAA) without skeletal or ocular features of the Marfan syndrome for defects in fibrillin synthesis or processing. Dermal fibroblasts obtained from biopsies were pulse labeled with [{sup 35}S]cysteine for 30 minutes and then chased for 0, 4, and 20 hours. The media, cell lysate and extracellular matrix were harvested separately, then analyzed by SDS-PAGE. We selected fibroblasts from 17 TAA patients to study based on the development of a TAA at a young age or a family history of TAAs. Cells from 3 patients synthesized and secreted fibrillin normally, but did not incorporate the fibrillin in the extracellular matrix. None of the cell strains were found to have diminished synthesis of fibrillin when compared with control cells. We were unable to detect abnormalities in the synthesis, secretion, or matrix incorporation of fibrillin by cells from 9 of the 17 patients. These results indicate that fibrillin protein defects are found in a significant number of patients with TAAs who are young or have a family history of TAAs. Analysis of the FBN1 gene for mutations in these patients with fibrillin protein defects will determine if the observed protein abnormalities are the result of FBN1 gene mutations.
- OSTI ID:
- 133972
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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