{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T02:16:15Z","timestamp":1781144175176,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,4,4]],"date-time":"2011-04-04T00:00:00Z","timestamp":1301875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Juvenile polyposis syndrome (JPS) is caused by heterozygous mutations in either <jats:italic>SMAD4<\/jats:italic> or <jats:italic>BMPR1A<\/jats:italic>. Individuals with JPS due to mutations in <jats:italic>SMAD4<\/jats:italic> are at greater risk to manifest signs of hereditary hemorrhagic telangiectasia (HHT). HHT is caused by either mutations in <jats:italic>SMAD4<\/jats:italic> or other genes that modulate transforming growth factor\u2010beta (TGF\u03b2) signaling. Additional genes in the TGF\u03b2 network include <jats:italic>FBN1<\/jats:italic>, <jats:italic>TGFBR1<\/jats:italic>, and <jats:italic>TGFBR2<\/jats:italic>, mutations of which cause either Marfan syndrome (MFS) or Loeys\u2013Dietz syndrome (LDS), respectively. As <jats:italic>SMAD4<\/jats:italic>, <jats:italic>FBN1<\/jats:italic>, and <jats:italic>TGFBR1\/2<\/jats:italic> map to different regions of the genome, disorders associated with mutations in these genes are not expected to co\u2010segregate in a family. We report an individual whose family history was positive for aortopathy, mitral valve dysfunction, and JPS. Mutation analysis of <jats:italic>SMAD4<\/jats:italic> implicates this gene for these phenotypes in this family. Although <jats:italic>SMAD4<\/jats:italic> is among several genes in the TGF\u03b2 network, and although prior single case reports have described large vessel aneurysms in HHT, this is the first description of aortic and mitral disease presenting with JPS. This observation suggests that, in addition to HHT, individuals with <jats:italic>SMAD4<\/jats:italic> mutations may be at risk for aortic dilation and mitral valve dysfunction. We emphasize the importance of comprehensive review of the medical history prior to molecular testing, especially in an asymptomatic patient. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33968","type":"journal-article","created":{"date-parts":[[2011,4,4]],"date-time":"2011-04-04T21:45:05Z","timestamp":1301953505000},"page":"1165-1169","source":"Crossref","is-referenced-by-count":57,"title":["<i>SMAD4<\/i> mutation segregating in a family with juvenile polyposis, aortopathy, and mitral valve dysfunction"],"prefix":"10.1002","volume":"155","author":[{"given":"Sara","family":"Andrabi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir Reza","family":"Bekheirnia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Robbins\u2010Furman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Alan","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Prior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Potocki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2009.08.058"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.30"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.suppl_1.1799"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907013410101"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15732-2"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33206"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5366.1086"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.018598"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.4065\/78.6.774"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2853"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.129932"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000151766"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055695"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072785"},{"key":"e_1_2_5_17_1","first-page":"15","article-title":"TGF\u2010beta dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome","volume":"11","author":"Ng CM","year":"2004","journal-title":"J Clin Invest"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-009-1482-4"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.05.038"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1178"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.6.1"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33968","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.33968","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33968","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T07:54:06Z","timestamp":1694678046000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4,4]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1002\/ajmg.a.33968"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33968","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4,4]]}}}