To examine the associations among fibrillin gene mutations, protein function, and Marfan syndrome phenotype, we screened for alterations in the fibrillin coding sequence in patients with a range of manifestations and clinical severity. A cysteine to serine substitution at codon 1409 (C1409S) was identified in an epidermal growth factor (EGF)-like motif from one fibrillin allele which segregates...

fibrillin-rich microfibrils are susceptible to degradation by serine proteases, and the amino acid substitutions found in Marfan syndrome change the fragmentation patterns. Fibrillin degradation products generated by MMP activity provide conclusive evidence that these enzymes cause specific changes to assembled microfibrils. In Marfan syndrome, most of the mutations in fibrillin-1 are found wit...

Mutations in the genes encoding fibrillin, an extracellular matrix protein involved in providing elastic properties to the connective tissues, may result in specific craniofacial and oral anomalies. A number of craniofacial (retrognathia, dolichocephaly, high palate) and dental (root deformity, pulp calcification) manifestations are considered pathognomic for the Marfan syndrome (MFS), a condit...

PURPOSE ADAMTSL4 mutations cause autosomal recessive isolated ectopia lentis (IEL) and ectopia lentis et pupillae. Dominant FBN1 mutations cause IEL or syndromic ectopia lentis (Marfan syndrome and Weill-Marchesani syndrome). The authors sought to characterize recombinant ADAMTSL4 and the ocular distribution of ADAMTSL4 and to investigate whether ADAMTSL4 influences the biogenesis of fibrillin-...

We have examined the existence and distribution of fibrillin-1 within the endometrium and decidua to ascertain the effect of decidualization upon its synthesis, and its relationship to other extracellular matrix proteins. Formalin-fixed, paraffin-embedded tissues were stained using monoclonal antibodies to collagen IV, elastin, fibrillin-1 and laminin, by immunocytochemistry. Fibrillin-1 was pr...

During the previous cloning of the fibrillin gene (FBN1), we isolated a partial cDNA coding for a fibrillin-like peptide and mapped the corresponding gene (FBN2) to human chromosome 5. (Lee, B., M. Godfrey, E. Vitale, H. Hori, M. G. Mattei, M. Sarfarazi, P. Tsipouras, F. Ramirez, and D. W. Hollister. 1991. Nature [Lond.]. 352:330-334). The study left, however, unresolved whether or not the FBN2...

The glycoprotein fibrillin is the principal component of the ciliary zonule and has an important role in the strength and elasticity of ocular connective tissues. Fibrillin polymers form the structural scaVold of extensible microfibrils which are present in ocular elastic tissues and are arranged in parallel bundles to form the zonular fibres. These fibrillin-rich microfibrils are morphological...

Microfibrils are macromolecular complexes associated with elastin to form elastic fibers that endow extensible tissues, such as arteries, lungs, and skin, with elasticity property. Fibrillin-1, the main component of microfibrils, is a 350-kDa glycoprotein for which genetic haploinsufficiency in humans can lead to Marfan syndrome, a severe polyfeatured pathology including aortic aneurysms and di...

Fibrillin-1 and -2 are large modular extracellular matrix glycoproteins found in many vertebrate organ systems and are known to be key components of the elastic fibre. In the present study, we identify a new heparin-binding region in fibrillin-2 between exons 18 and 24. Additionally, we have narrowed the location of heparin-binding activity previously identified in fibrillin-1 to the last 17 re...

The expression and assembly of the microfibrillar glycoprotein fibrillin has been investigated in cultures of nuchal ligament fibroblasts, skin fibroblasts and vascular smooth muscle cells. The level of fibrillin expression varied with the cell type and growth conditions. Higher levels of synthesis were recorded in quiescent post-confluent cells than in actively dividing subconfluent cultures. ...