{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:14:56Z","timestamp":1790522096877,"version":"4.1.0"},"reference-count":50,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[1999,10,1]],"date-time":"1999-10-01T00:00:00Z","timestamp":938736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T00:00:00Z","timestamp":1374192000000},"content-version":"vor","delay-in-days":5040,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[1999,10]]},"DOI":"10.1086\/302582","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:47:41Z","timestamp":1027694861000},"page":"1007-1020","source":"Crossref","is-referenced-by-count":182,"title":["Cysteine Substitutions in Epidermal Growth Factor\u2013Like Domains of Fibrillin-1: Distinct Effects on Biochemical and Clinical Phenotypes"],"prefix":"10.1016","volume":"65","author":[{"given":"I.","family":"Schrijver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Brenn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Furthmayr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Francke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1086\/302582_bib1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1136\/jmg.33.8.665","article-title":"Characterisation of four novel fibrillin-1 (FBN1) mutations in Marfan syndrome","volume":"33","author":"Ades","year":"1996","journal-title":"J Med Genet"},{"key":"10.1086\/302582_bib3","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1172\/JCI117298","article-title":"Quantitative differences in biosynthesis and extracellular deposition of fibrillin in cultured fibroblasts distinguish five groups of Marfan syndrome patients and suggest distinct pathogenetic mechanisms","volume":"94","author":"Aoyama","year":"1994","journal-title":"J Clin Invest"},{"key":"10.1086\/302582_bib4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/ajmg.1320580216","article-title":"Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders","volume":"58","author":"Aoyama","year":"1995","journal-title":"Am J Med Genet"},{"key":"10.1086\/302582_bib2","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":"1993","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib5","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s004390050489","article-title":"A novel de novo mutations in exon 14 of the fibrillin-1 gene associated with delayed secretion of fibrillin in a patient with a mild Marfan phenotype","volume":"100","author":"Booms","year":"1997","journal-title":"Hum Genet"},{"key":"10.1086\/302582_bib6","first-page":"389","article-title":"Dermal fibroblast culture as a model for studies of fibrillin assembly and pathogenetic mechanisms: defects in distinct groups of individuals with Marfan's syndrome","volume":"75","author":"Brenn","year":"1996","journal-title":"Lab Invest"},{"key":"10.1086\/302582_bib7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0959-440X(05)80111-3","article-title":"Epidermal growth factor-like modules","volume":"3","author":"Campbell","year":"1993","journal-title":"Curr Opin Struct Biol"},{"key":"10.1086\/302582_bib8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/nar\/26.1.229","article-title":"Marfan database (third edition): new mutations and new routines for the software","volume":"26","author":"Collod-Beroud","year":"1998","journal-title":"Nucleic Acids Res"},{"key":"10.1086\/302582_bib9","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1006\/geno.1993.1350","article-title":"Fibrillin binds calcium and is coded by cDNAs that reveal a multidomain structure and alternatively spliced exons at the 5\u2032 end","volume":"17","author":"Corson","year":"1993","journal-title":"Genomics"},{"key":"10.1086\/302582_bib10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R","article-title":"Revised diagnostic criteria for the Marfan syndrome","volume":"62","author":"De Paepe","year":"1996","journal-title":"Am J Med Genet"},{"key":"10.1086\/302582_bib11","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/352337a0","article-title":"Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene","volume":"352","author":"Dietz","year":"1991","journal-title":"Nature"},{"key":"10.1086\/302582_bib14","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/hmg\/4.suppl_1.1799","article-title":"Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders","volume":"4","author":"Dietz","year":"1995","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib12","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1172\/JCI115766","article-title":"Marfan phenotype variability in a family segregating a missense mutation in the epidermal growth factor-like motif of the fibrillin gene","volume":"89","author":"Dietz","year":"1992","journal-title":"J Clin Invest"},{"key":"10.1086\/302582_bib13","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/humu.1380010504","article-title":"Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains","volume":"1","author":"Dietz","year":"1992","journal-title":"Hum Mutat"},{"key":"10.1086\/302582_bib15","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0092-8674(00)81259-3","article-title":"Solution structure of a pair of calcium-binding epidermal growth factor-like domains: Implications for the Marfan syndrome and other genetic disorders","volume":"85","author":"Downing","year":"1996","journal-title":"Cell"},{"key":"10.1086\/302582_bib16","first-page":"191","article-title":"Ascending aortic aneurysm with or without features of Marfan syndrome and other fibrillinopathies: new insights","volume":"9","author":"Furthmayr","year":"1997","journal-title":"Sem Thorac Cardiovasc Surg"},{"key":"10.1086\/302582_bib17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/nar\/26.1.265","article-title":"Haemophilia B: database of point mutations and short additions and deletions\u2014eighth edition","volume":"26","author":"Giannelli","year":"1998","journal-title":"Nucleic Acids Res"},{"key":"10.1086\/302582_bib18","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.1093\/nar\/17.20.8093","article-title":"Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumor-progression markers","volume":"17","author":"Haliassos","year":"1989","journal-title":"Nucleic Acids Res"},{"key":"10.1086\/302582_bib19","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/j.1460-2075.1990.tb08133.x","article-title":"The first EGF-like domain from human factor IX contains a high-affinity calcium binding site","volume":"9","author":"Handford","year":"1990","journal-title":"EMBO J"},{"key":"10.1086\/302582_bib22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/(SICI)1098-1004(1997)10:6<415::AID-HUMU1>3.0.CO;2-C","article-title":"Fibrillin-1 mutations in Marfan syndrome and other type-1 fibrillinopathies","volume":"10","author":"Hayward","year":"1997","journal-title":"Hum Mutat"},{"key":"10.1086\/302582_bib21","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/(SICI)1098-1004(1997)10:4<280::AID-HUMU3>3.0.CO;2-L","article-title":"Mutation screening of all 65 exons of the fibrillin-1 gene in 60 patients with Marfan syndrome: report of 12 novel mutations","volume":"10","author":"Hayward","year":"1997","journal-title":"Hum Mutat"},{"key":"10.1086\/302582_bib20","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/hmg\/3.2.373","article-title":"Two novel mutations and a neutral polymorphism in EGF-like domains of the fibrillin gene (FBN1): SSCP screening of exons 15-21 in Marfan syndrome patients","volume":"3","author":"Hayward","year":"1994","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib23","first-page":"447","article-title":"Differential allelic expression of a fibrillin gene (FBN1) in patients with Marfan syndrome","volume":"55","author":"Hewett","year":"1994","journal-title":"Am J Hum Genet"},{"key":"10.1086\/302582_bib24","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/jmg.31.4.338","article-title":"A new missense mutation of fibrillin in a patient with Marfan syndrome","volume":"31","author":"Hewett","year":"1994","journal-title":"J Med Genet"},{"key":"10.1086\/302582_bib25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/ng0194-64","article-title":"Mutations in the fibrillin gene responsible for dominant ectopia lentis and neonatal Marfan syndrome","volume":"6","author":"Kainulainen","year":"1994","journal-title":"Nat Genet"},{"key":"10.1086\/302582_bib26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0014-5793(93)80829-J","article-title":"The role of calcium in the organization of fibrillin microfibrils","volume":"336","author":"Kielty","year":"1993","journal-title":"FEBS Lett"},{"key":"10.1086\/302582_bib27","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1006\/geno.1995.1042","article-title":"Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C)","volume":"27","author":"Lappalainen","year":"1995","journal-title":"Genomics"},{"key":"10.1086\/302582_bib28","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/hmg\/5.10.1581","article-title":"Mutant fibrillin-1 monomers lacking EGF-like domains disrupt microfibril assembly and cause severe Marfan syndrome","volume":"5","author":"Liu","year":"1996","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib29","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ng0897-328","article-title":"Silent mutation induces exon skipping of fibrillin-1 gene in Marfan syndrome","volume":"16","author":"Liu","year":"1997","journal-title":"Nat Genet"},{"key":"10.1086\/302582_bib30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1089\/gte.1997.1.237","article-title":"Denaturing HPLC-identified novel FBN1 mutations, polymorphisms, and sequence variants in Marfan syndrome and related connective tissue disorders","volume":"1","author":"Liu","year":"1998","journal-title":"Genet Test"},{"key":"10.1086\/302582_bib31","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1006\/geno.1996.0492","article-title":"A point mutation creating an extra N-glycosylation site in fibrillin-1 results in neonatal Marfan syndrome","volume":"36","author":"Lonnqvist","year":"1996","journal-title":"Genomics"},{"key":"10.1086\/302582_bib32","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/352334a0","article-title":"Partial sequence of a candidate gene for the Marfan syndrome","volume":"352","author":"Maslen","year":"1991","journal-title":"Nature"},{"key":"10.1086\/302582_bib33","first-page":"A339","article-title":"Fibrillin (FBN1) mutations in the \u201cneonatal region\u201d: toward genotype\/phenotype correlations in neonatal Marfan syndrome","volume":"57","author":"Mathews","year":"1995","journal-title":"Am J Hum Genet Suppl"},{"key":"10.1086\/302582_bib34","first-page":"684","article-title":"The eye in the Marfan syndrome","volume":"79","author":"Maumenee","year":"1981","journal-title":"Trans Am Ophthalmol Soc"},{"key":"10.1086\/302582_bib36","first-page":"447","article-title":"Severe neonatal Marfan syndrome resulting from a de novo 3-bp insertion into the fibrillin gene on chromosome 15","volume":"54","author":"Milewicz","year":"1994","journal-title":"Am J Hum Genet"},{"key":"10.1086\/302582_bib37","first-page":"8","article-title":"Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons","volume":"57","author":"Nijbroek","year":"1995","journal-title":"Am J Hum Genet"},{"key":"10.1086\/302582_bib38","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/0888-7543(89)90129-8","article-title":"Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction","volume":"5","author":"Orita","year":"1989","journal-title":"Genomics"},{"key":"10.1086\/302582_bib39","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1006\/jmcc.1997.0426","article-title":"A major involvement of the cardiovascular system in patients affected by Marfan syndrome: novel mutations in fibrillin 1 gene","volume":"29","author":"Pepe","year":"1997","journal-title":"J Mol Cell Cardiol"},{"key":"10.1086\/302582_bib40","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/hmg\/2.7.961","article-title":"Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome","volume":"2","author":"Pereira","year":"1993","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib41","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1093\/hmg\/3.6.1013","article-title":"Substitution of a cysteine residue in a non-calcium binding, EGF-like domain of fibrillin segregates with the Marfan syndrome in a large kindred","volume":"3","author":"Piersall","year":"1994","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib42","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<233::AID-AJMG7>3.0.CO;2-U","article-title":"Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene","volume":"62","author":"Putnam","year":"1996","journal-title":"Am J Med Genet"},{"key":"10.1086\/302582_bib43","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1056\/NEJM197904053001406","article-title":"The Marfan syndrome: diagnosis and management","volume":"300","author":"Pyeritz","year":"1979","journal-title":"N Engl J Med"},{"key":"10.1086\/302582_bib44","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0092-8674(95)90059-4","article-title":"The structure of a Ca-binding epidermal growth factor-like domain: its role in protein-protein interactions","volume":"82","author":"Rao","year":"1995","journal-title":"Cell"},{"key":"10.1086\/302582_bib45","doi-asserted-by":"crossref","first-page":"7368","DOI":"10.1074\/jbc.272.11.7368","article-title":"Calcium determines the shape of fibrillin","volume":"272","author":"Reinhardt","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1086\/302582_bib46","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1074\/jbc.272.2.1231","article-title":"Calcium stabilizes fibrillin-1 against proteolytic degradation","volume":"272","author":"Reinhardt","year":"1997","journal-title":"J Biol Chem"},{"key":"10.1086\/302582_bib47","first-page":"1085","article-title":"Screening for 185delAG in the Ashkenazim","volume":"60","author":"Richards","year":"1997","journal-title":"Am J Hum Genet"},{"key":"10.1086\/302582_bib48","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1083\/jcb.103.6.2499","article-title":"Fibrillin, a new 350-kD glycoprotein is a component of extracellular microfibrils","volume":"103","author":"Sakai","year":"1986","journal-title":"J Cell Biol"},{"key":"10.1086\/302582_bib49","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1093\/hmg\/2.11.1813","article-title":"Mutation screening of complete fibrillin-1 coding sequence: report of five new mutations, including two in 8-cysteine domains","volume":"2","author":"Tynan","year":"1993","journal-title":"Hum Mol Genet"},{"key":"10.1086\/302582_bib50","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/nar\/26.1.248","article-title":"LDLR database (second edition): new additions to the database and software, and results of the first molecular analysis","volume":"26","author":"Varret","year":"1998","journal-title":"Nucleic Acids Res"},{"key":"10.1086\/302582_bib51","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/(SICI)1098-1004(1997)9:4<359::AID-HUMU10>3.0.CO;2-1","article-title":"Three novel fibrillin mutations in exon 25 and 27: classic versus neonatal Marfan syndrome","volume":"9","author":"Wang","year":"1997","journal-title":"Hum Mutat"}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929707626032?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929707626032?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T23:44:19Z","timestamp":1583279059000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929707626032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,10]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1999,10]]}},"alternative-id":["S0002929707626032"],"URL":"https:\/\/doi.org\/10.1086\/302582","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[1999,10]]}}}