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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Skin collagen from fifteen patients with idiopathic adolescent scoliosis, three with congenital scoliosis, and fourteen patients with various degrees of Marfan's syndrome has been examined. 2. The stability of a polymeric collagen fraction, extracted from the skin of these patients, to depolymerization, has been compared with that from thirty-one matched control subjects. 3. The mean polymeric collagen stability was significantly reduced (P less than 0-01) in the group of fifteen patients with idiopathic adolescent scoliosis. The individual reductions in stability were greater in the younger patients and no reduction was found in two patients aged 19 years who had a mature skeleton. 4. The mean stability of polymeric skin collagen from the group of patients with Marfan's syndrome was not significantly abnormal, although there were individual low values. 5. Polymeric collagen of low stability was present in individual patients from each clinical group. Instability of collagen (from whatever cause) at a time of rapid growth may contribute to the high incidence of scoliosis in adolescent girls. In boys, adolescent scoliosis is less common and the maximum growth rate occurs at a time when collagen stability is less reduced.
Clin Sci Mol Med 1976 Nov
PMID:Skin collagen in idiopathic adolescent scoliosis and Marfan's syndrome. 99 44

Samples from the ascending aortae from two calves affected by bovine Marfan syndrome were subjected to biochemical analyses of the connective tissue and were compared to age-matched controls. Elastin was extracted from the aortic samples with 5 M guanidine-HCl, bacterial collagenase digestion, and dithiothreitol reduction. Amino acid analysis revealed that desmosine and isodesmosine levels were the same in Marfan calves as in control animals. Gravimetric measurements of elastin, amino acid composition, soluble protein, and uronic acid values also showed no significant difference between Marfan and control tissue. In contrast to elastin, collagen in aortae of Marfan calves was significantly higher than the mean of several controls. These findings, along with other observations of this animal model, support the conclusion that the microscopic and biochemical lesions of aortic elastin in bovine Marfan syndrome likely result from defective microfibrillar metabolism. Absence of cystic medial necrosis in bovine Marfan aortae may explain normal elastin content in the animal model.
Exp Mol Pathol 1992 Oct
PMID:Normal elastin content of aorta in bovine Marfan syndrome. 142 58

Elastin and collagen concentrations were determined in intimal-medial samples of ascending aortas from healthy controls of different ages and from 20 patients with annuloaortic ectasia (AAE). Five patients had the Marfan syndrome. In controls the highest elastin concentrations (estimated from desmosine concentrations or insoluble residues after hot-alkali extraction) were found in children. During aging until 60 years, elastin concentration decreased when determined by the hot-alkali extraction method while desmosine concentration changed less. Aorta samples from the Marfan-syndrome patients showed a great variation of elastin concentration from total lack to normal values. Samples from the other AAE patients could be divided into two groups. One contained clearly less elastin and more collagen than the controls whereas in the other group this difference was less marked. Histological examination of the aortic wall of the first group also showed marked fibrosis accompanied by severe elastin fragmentation and acellularity. From the 15 non-Marfan patients 14 were men. By means of clinical examination these patients could also be divided into "familial" and "nonfamilial" groups, because increased diameter of the aortic root was found in relatives of almost half of the patients. However, there were no differences in elastin and collagen concentrations between the familial and nonfamilial cases. As well, no correlation was found between biochemical findings and diameters of the aortic roots. These results point to altered elastin and/or collagen metabolism in the aortic wall of AAE patients.
Exp Mol Pathol 1985 Aug
PMID:Elastin and collagen in the aortic wall: changes in the Marfan syndrome and annuloaortic ectasia. 400 38

The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue. Variable and pleiotropic clinical features are observed in the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum of this disorder comprises a group of patients usually diagnosed at birth, who have a life expectancy of little more than a year. To distinguish this group of patients from those with classical MFS, we refer to them as neonatal Marfan syndrome (nMFS). These infants usually die of congestive heart failure rather than aortic aneurysmal disease, the most frequent cause of morbidity and mortality in classical MFS. Defects in fibrillin, an elastin-associated microfibrillar glycoprotein, are now known to cause both the classical and neonatal forms of MFS. Here we report the recurrent mis-splicing of fibrillin (FBN1) exon 32, a precursor EGF-like calcium binding domain, in two unrelated infants with nMFS. The mis-splicing, in one patient, was due to an A-->T transversion at the -2 position of the consensus acceptor splice site; while that in the second patient was caused by a G-->A transition at the +1 position of the donor splice site. Characterization of FBN1 mutations in individuals at the most severe end of the Marfan syndrome spectrum should provide greater understanding of the multiple domains and regions of fibrillin.
Hum Mol Genet 1995 Apr
PMID:Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome. 763 9

We studied profibrillin-1 (proFib) synthesis and microfibril formation in cultured fibroblasts from an individual with severe Marfan syndrome harboring a premature stop codon (W2756ter) in one FBN1 allele. Rotary shadowing analysis of extracellular matrix produced by these cells revealed the presence of only a very few intact microfibrils which showed marked disorganisation within the interbeaded domains. Metabolic pulse-chase studies identified intracellularly a population of truncated proFib molecules which were secreted more slowly than the normal proFib derived from the normal allele. Culture media contained strikingly reduced amounts of wild-type proFib in comparison to fibrillin (Fib). Our findings imply that (1) the truncated proFib is secreted and disturbs microfibril assembly; (2) the mutation is probably close to a putative cleavage site in the proFib C terminus necessary for the conversion of proFib to Fib; (3) the truncated proFib is over-N-glycosylated due to intracellular retention rather than incomplete cleavage of proFib with persistence of N-glycosylated sites; (4) not all potential N-glycosylation sites in proFib seem to be normally used, since we could produce over-N-glycosylated proFib in normal cells by brefeldin A mediated intracellular captivation and subsequent appearance of over-glycosylated Fib in culture medium upon removal of the compound. It is conceivable that post-translational over-modification might be important for modulating the phenotype of FBN1 mutations in Marfan syndrome.
J Mol Biol 1995 May 19
PMID:Truncated profibrillin of a Marfan patient is of apparent similar size as fibrillin: intracellular retention leads to over-N-glycosylation. 776 Mar 31

Mutations of the fibrillin gene (FBN1) are known to cause classical Marfan's syndrome, ectopia lentis and neonatal Marfan's syndrome. We have identified a novel missense mutation in exon 28 of the FBN1 gene (R1170H) which is responsible for an atypical marfanoid phenotype characterised by dolichostenomelia and arachnodactyly.
Mol Cell Probes 1994 Aug
PMID:A novel mutation in the fibrillin gene (FBN1) in familial arachnodactyly. 787 75

Dermal fibroblasts from nine Marfan syndrome patients with missense mutations in the fibrillin-1 gene (FBN1) produced nearly normal amounts of fibrillin as determined by quantitative pulse-chase experiments. However, six of the seven mutations involving substitutions of highly conserved cysteine residues exhibited lower rates of intracellular transport and secretion. This effect is likely due to improper folding, since intracellular fibrillin processing was also affected by the reducing agent dithiothreitol. Normal secretion patterns were seen in three mutations that either change the conformation of EGF-like domains or change consensus amino acids required for Ca(++)-binding. In all nine fibroblasts strains, however, the deposition of fibrillin in the extracellular matrix was reduced to 50% of normal in two and to less than 30% in seven of the nine samples studied. The protein alterations caused by these missense mutations are associated with moderate to severe features of Marfan syndrome and a dominant negative mechanism is suggested to play a major role in their pathogenesis.
Hum Mol Genet 1993 Dec
PMID:Missense mutations impair intracellular processing of fibrillin and microfibril assembly in Marfan syndrome. 811 84

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder characterized by cardiovascular, ocular and skeletal manifestations. Previously, mutations in the fibrillin-1 gene on chromosome 15 (FBN1) have been reported to cause MFS. We have now screened 44 probands with MFS or related phenotypes for alterations in the entire fibrillin coding sequence (9.3 kb) by single strand conformation analysis. We report four unique mutations in the fibrillin gene of unrelated MFS patients. One is a 17 bp deletion and three are missense mutations, two of which involve 8-cysteine motifs. Another missense mutation was found in two unrelated individuals with annuloaortic ectasia but was also present in unaffected relatives and controls from various ethnic backgrounds. By using allele-specific oligonucleotide hybridization, we screened 65 unrelated MFS patients, 29 patients with related phenotypes and 84 control individuals for these mutations as well as for a previously reported mutation and two polymorphisms. Our results suggest that most MFS families carry unique mutations and that the fibrillin genotype is not the sole determinant of the connective tissue phenotype.
Hum Mol Genet 1993 Nov
PMID:Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cysteine domains. 828 Nov 41

Marfan syndrome results from mutations in an extracellular matrix glycoprotein, fibrillin. Previous studies have characterized approximately 6.9-kb of the estimated 10-kb fibrillin transcript. We have now completed the primary structure of fibrillin, elucidated the exon/intron organization of the gene and derived a physical map of the genetic locus. Pre-fibrillin consists of 2,871 amino acids which, excluding the signal peptide, are arranged into five structurally distinct regions. The largest of these regions comprises about 75% of the entire protein and consists of numerous repeated cysteine-rich sequences homologous to the peptide motifs of the epidermal growth factor (EGF) and transforming growth factor-beta binding protein (TGF-bp). Forty-three of the forty-six EGF-like repeats contain a calcium binding consensus sequence (EGF-CB) conceivably mediating protein-protein interactions. Fibrillin exhibits a few additional cysteine-rich modules that are apparently unique to this macromolecule and may represent evolutionary variants of the EGF-CB and TGF-bp motifs. Almost all of the cysteine-rich repeats are encoded by single exons; consequently, the fibrillin gene is relatively large (approximately 110-kb) and highly fragmented (65 exons). This study provides the first comprehensive analysis of the fibrillin gene and relevant information for the full characterization of Marfan syndrome mutations.
Hum Mol Genet 1993 Jul
PMID:Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. 826 58

The K-fgf/hst oncogene encodes a growth factor of the fibroblast growth factor (FGF) family and transforms cells through an autocrine mechanism which requires extracellular activation of its receptor(s). To identify the cell and tissue targets of K-fgf oncogenic potential in vivo, we constructed a recombinant retrovirus carrying the human K-fgf cDNA and injected it, together with helper Moloney murine leukemia virus, into immunocompetent as well as nude mice. The original construct was highly transforming in tissue culture but produced no detectable pathologies in vivo with the exception of a single fibrosarcoma which arose after a long latency. The virus produced by this tumor appears to have undergone a complex series of recombination events involving the helper Moloney murine leukemia virus. It encodes an Env/K-FGF fusion protein whose expression is under the control of a hybrid long terminal repeat. This virus (designated MFS, for meningeal fibrosarcoma) induces tumors in mice with high frequency and short latency. These neoplasms consist of aggressive fibrosarcomas of soft tissue as well as diffuse meningeal tumors originating from the dura mater that surround the whole central nervous system and cause severe hydrocephalus. The Env/K-FGF fusion protein expressed by the MFS virus has retained all of the biological properties of native K-FGF, including secretion, mitogenic activity, heparin binding, and neutralization by anti-K-FGF antibodies. These and other results indicate that the tumors induced by the MFS virus result from the oncogenic potential of K-FGF.
Mol Cell Biol 1993 Apr
PMID:A retrovirus carrying the K-fgf oncogene induces diffuse meningeal tumors and soft-tissue fibrosarcomas. 845 94


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