Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts

Michael Raghunath, Andrea Superti-Furga, Maurice Godfrey, Beat Steinmann

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Abnormalities of the microfibrillar protein fibrillin (Fib) have been reported in Marfan syndrome (MFS). The so-called neonatal Marfan syndrome (nMFS) is a lethal phenotype displaying features that are not seen in classical MFS. We have therefore studied the biosynthesis and extracellular deposition of Fib and decorin in fibroblasts from a patient with nMFS and controls. Immunofluorescence of the patient's cell cultures showed an almost complete absence of Fib and a marked reduction of decorin in the extracellular matrix (ECM). The nMFS skin revealed Fib on subbasal microfibrillar bundles in the papillary dermis, and Fib associated with elastic fibers in the reticular dermis; the bundles and fibers were fragmented and thinner than normal. Pulse-chase labeling of cells with [35S]Met/Cys revealed moderately reduced secretion, but a diminished deposition of Fib in the ECM; this was more apparent at a longer chase time. Fib mRNA and synthesis appeared to be normal, where-as both decorin mRNA and biosynthesis were reduced. We therefore assume a structural Fib defect in this patient causing reduced deposition into and/or enhanced removal from the ECM, whereas the reduced decorin biosynthesis may be a secondary regulatory phenomenon. The clinical relevance of this remains unclear. Our findings imply that Fib defects may be responsible for the severe, complex phenotype of nMFS.

Original languageEnglish (US)
Pages (from-to)511-515
Number of pages5
JournalHuman genetics
Volume90
Issue number5
DOIs
StatePublished - Jan 1993

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts'. Together they form a unique fingerprint.

Cite this