{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:49:19Z","timestamp":1788238159835,"version":"build-2803163510"},"reference-count":43,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[1995,3,1]],"date-time":"1995-03-01T00:00:00Z","timestamp":794016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Mutations in the FBN1 gene encoding the microfibrillar glycoprotein fibrillin cause Marfan syndrome, a relatively common autosomal dominant connective tissue disease. Causative FBN1 mutations appear to be dispersed throughout the coding frame, and to date no predictable genotype: phenotype correlations have emerged. We have identified a point mutation within an eight-cysteine \u2018hybrid\u2019 motif of the fibrillin polypeptide which results in the substitution of an arginine for a cysteine, in a patient severely affected in the cardiovascular, skeletal and ocular systems.<\/jats:p>\n               <jats:p>We have utilised cell cultures from various tissues of this patient to investigate the effects of this mutation on fibrillin expression and deposition, and the consequences in terms of microfibril assembly and organisation. We have established that there is no difference in the expression of normal and mutant alleles, and fibrillin synthesis, secretion and deposition are also normal. However, the rate of fibrillin aggregation is reduced and microfibrillar assemblies are both remarkably scarce and morphologically abnormal.<\/jats:p>\n               <jats:p>These data clearly demonstrate that the mutated allele interferes with normal assembly, and strongly implicate this particular region of the fibrillin-1 molecule in stabilising microfibrillar assemblies.<\/jats:p>","DOI":"10.1242\/jcs.108.3.1317","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T16:16:17Z","timestamp":1619367377000},"page":"1317-1323","source":"Crossref","is-referenced-by-count":20,"title":["Cysteine-to-arginine point mutation in a \u2018hybrid\u2019 eight-cysteine domain of FBN1: consequences for fibrillin aggregation and microfibril assembly"],"prefix":"10.1242","volume":"108","author":[{"given":"Cay M.","family":"Kielty","sequence":"first","affiliation":[{"name":"University of Manchester, Oxford Road 1 School of Biological Sciences, Stopford Building 2.205 , , Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terhi","family":"Rantam\u00e4ki","sequence":"additional","affiliation":[{"name":"2 Department of Human Molecular Genetics, National Public Health Institute, FIN-00300 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne H.","family":"Child","sequence":"additional","affiliation":[{"name":"3 Heart Science Centre and National Heart and Lung Institute, Harefield Hospital, Middlesex UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Adrian","family":"Shuttleworth","sequence":"additional","affiliation":[{"name":"University of Manchester, Oxford Road 1 School of Biological Sciences, Stopford Building 2.205 , , Manchester M13 9PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leena","family":"Peltonen","sequence":"additional","affiliation":[{"name":"2 Department of Human Molecular Genetics, National Public Health Institute, FIN-00300 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1995,3,1]]},"reference":[{"key":"2023122401044683100_JOCES_108_3_1317C1","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1093\/hmg\/2.12.2135","article-title":"Missense mutations impair intracellular processing of fibrillin and microfibril assembly in Marfan syndrome","volume":"2","author":"Aoyama","year":"1994","journal-title":"Hum. Mol. 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Invest"},{"key":"2023122401044683100_JOCES_108_3_1317C7","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1126\/science.8430317","article-title":"The skipping of constitutive exons in vivo induced by nonsense mutations","volume":"259","author":"Dietz","year":"1993","journal-title":"Science"},{"key":"2023122401044683100_JOCES_108_3_1317C8","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1006\/geno.1993.1349","article-title":"Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome","volume":"17","author":"Dietz","year":"1993","journal-title":"Genomics"},{"key":"2023122401044683100_JOCES_108_3_1317C9","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/1523-1747.ep12483132","article-title":"Elastin-associated microfibrils (10 nm) in a three-dimensional fibroblast culture","volume":"97","author":"Fleischmajer","year":"1991","journal-title":"J. Invest. Dermatol"},{"key":"2023122401044683100_JOCES_108_3_1317C10","doi-asserted-by":"crossref","first-page":"7596","DOI":"10.1016\/S0021-9258(20)89489-7","article-title":"Complementary DNA cloning establishes microfibril-associated glycoprotein (MAGP) to be a discrete component of elastin-associated microfibrils","volume":"266","author":"Gibson","year":"1991","journal-title":"J. Biol. Chem"},{"key":"2023122401044683100_JOCES_108_3_1317C11","first-page":"662","article-title":"Prenatal diagnosis and a donor splice site mutation in fibrillin in a family with Marfan syndrome","volume":"49","author":"Godfrey","year":"1993","journal-title":"Am. J. Hum. Genet"},{"key":"2023122401044683100_JOCES_108_3_1317C12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/humu.1380030212","article-title":"Identification of a novel nonsense mutation in the fibrillin gene (FBN1) using nonisotopic techniques","volume":"3","author":"Hayward","year":"1994","journal-title":"Hum. 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