{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:33:39Z","timestamp":1794000819020,"version":"4.8.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2010,2,4]],"date-time":"2010-02-04T00:00:00Z","timestamp":1265241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>Chao S\u2010C, Chen J\u2010S, Tsai C\u2010H, Lin JY\u2010M, Lin Y\u2010J, Sun HS. Novel exon nucleotide substitution at the splice junction causes a neonatal Marfan syndrome.<\/jats:p><jats:p>The fibrillin\u20101 gene (<jats:italic>FBN1<\/jats:italic>) mutations are associated with a broad spectrum of disorders including Marfan syndrome (MFS) and show great clinical heterogeneity. An underrepresentation for mutations leading to premature termination codon (PTC) in <jats:italic>FBN1<\/jats:italic> exons 24\u201332 was found in neonatal or severe MFS but the underlying cause was unclear. This study thoroughly examined two <jats:italic>FBN1<\/jats:italic> mutations on exons 24\u201332 region to illustrate the molecular mechanisms underlying these <jats:italic>FBN1<\/jats:italic> mutations on MFS etiology. Two nucleotide substitutions, c.3208G&gt; C, the last nucleotide of exon 26, and c.3209A&gt;G, the first nucleotide of exon 27, affecting the same amino acid, p.D1070H and p.D1070G, respectively, gave very different phenotypes. We demonstrate that c.3208G&gt;C generates two alternatively spliced transcripts, while c.3209A&gt;G does not affect the splicing. We further demonstrate that the aberrantly spliced transcripts do not go through nonsense\u2010mediated decay, but rather produce unstable, premature protein peptides that are degraded by endoplasmic reticulum associated degradation. The molecular mechanism outlined here defines a model for the pathogenesis of PTC\u2010containing mutation within the exons 24\u201332 of <jats:italic>FBN1<\/jats:italic> in MFS. Furthermore, our data suggest that PTC mutation within this region may lead to early lethality in neonatal MFS.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2009.01337.x","type":"journal-article","created":{"date-parts":[[2010,2,4]],"date-time":"2010-02-04T07:13:12Z","timestamp":1265267592000},"page":"453-463","source":"Crossref","is-referenced-by-count":10,"title":["Novel exon nucleotide substitution at the splice junction causes a neonatal Marfan syndrome"],"prefix":"10.1111","volume":"77","author":[{"given":"S\u2010C","family":"Chao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u2010S","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u2010H","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JY\u2010M","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y\u2010J","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HS","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,4,9]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.51.1.481"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.550207.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.6.2499"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/520125"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.207"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10054"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.156.11.1081"},{"key":"e_1_2_6_9_2","first-page":"8","article-title":"Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons","volume":"57","author":"Nijbroek G","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.1997.4.311"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(91)90380-O"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/1066527041410418"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074428"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02251-05"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm402"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki811"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.050106.093909"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.2.99"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00729.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(02)00358-7"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10249"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl535"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg775"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.5196404"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki811"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4512-08.2009"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.12.2135"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1349"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420641"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-007-0371-x"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.32.19489"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.11.7368"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2009.01337.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2009.01337.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:18:45Z","timestamp":1698751125000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2009.01337.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,9]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,5]]}},"alternative-id":["10.1111\/j.1399-0004.2009.01337.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2009.01337.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,9]]}}}