{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:09:56Z","timestamp":1780535396919,"version":"3.54.1"},"reference-count":37,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:p>It is now well established that defects in fibrillin-1 (FBN1) cause the variable and pleiotropic features of Marfan syndrome (MFS) and, at the most severe end of its clinical spectrum, neonatal Marfan syndrome (nMFS). Patients with nMFS have mitral and tricuspid valve involvement and aortic root dilatation, and die of congestive heart failure, often in the first year of life. Although mutations in classical MFS have been observed along the entire length of the FBN1 mRNA, mutations in nMFS appear to cluster in a relatively small region of FBN1, approximately between exons 24 and 34. Here we describe the appearance of two FBN1 mutations in a single allele of an infant with nMFS. The changes were within six bases of each other in exon 26. One was a T3212G transversion resulting in an I1071S amino acid substitution and the second was an A3219T transversion resulting in an E1073D amino acid substitution. This is the first reported double mutant allele in FBN1.<\/jats:p>","DOI":"10.1136\/jmg.33.9.760","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"760-763","source":"Crossref","is-referenced-by-count":23,"title":["Double mutant fibrillin-1 (FBN1) allele in a patient with neonatal Marfan syndrome."],"prefix":"10.1136","volume":"33","author":[{"given":"M","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Kishnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Decker-Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S G","family":"Kahler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y T","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Godfrey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/hmg\/4.7.1169","article-title":"Double mutant alleles: are they rare?","volume":"4","author":"Savov, A.; Angelicheva, D.; Balassopoulou, A.","year":"1995","unstructured":"Savov A, Angelicheva D, Balassopoulou A, et al. 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Hum Mutat 1992;1:366-74.","journal-title":"Hum Mutat"},{"key":"ref_19","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, H.C.; Valle, D.; Francomano, C.A.","year":"1993","unstructured":"Dietz HC, Valle D, Francomano CA, et al. The skipping of constitutive exons in vivo induced by nonsense mutations. Science 1993;259:680-3.","journal-title":"Science"},{"key":"ref_20","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, H.C.; McIntosh, I.; Sakai, L.Y.","year":"1993","unstructured":"Dietz HC, McIntosh I, Sakai LY, et al. 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Am J Hum Genet 1994;54:447-53.","journal-title":"on chromosome 15. Am J Hum Genet"},{"key":"ref_24","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, K.; Karttunen, L.; Puhakka, L.; Sakai, L.; Peltonen, L.","year":"1994","unstructured":"Kainulainen K, Karttunen L, Puhakka L, Sakai L, Peltonen L. Mutations in the fibrillin gene responsible for dominant ectopia lentis and neonatal Marfan syndrome. Nature Genet 1994;6:64-9.","journal-title":"Nature Genet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1093\/hmg\/4.4.607","article-title":"Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome","volume":"4","author":"Wang, M.; Price, C.E.; Han, J.","year":"1995","unstructured":"Wang M, Price CE, Han J, et al. 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