{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:42:09Z","timestamp":1790430129058,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"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":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Truncus arteriosus accounts for approximately 1% of congenital heart defects and the cause of isolated non\u2010syndromic truncus arteriosus is largely unknown. In order to identify the underlying molecular defect in a consanguineous family with recurrent tuncus arteriosus, homozygosity mapping followed by whole exome sequencing was performed. This resulted in the identification of a homozygous mutation, Arg1299Cys, in the\n                      <jats:italic>PLXND1<\/jats:italic>\n                      gene. The mutation affected a highly conserved residue, segregated with the disease in the family and was absent from available SNP databases and ethnic matched controls. in silico comparative modeling revealed that the mutation resides in the N\u2010terminal segment of the human plexin\u2010D1 intracellular region which interacts with the catalytic GTPase\u2010activating protein homology region. The mutation likely destabilizes the intracellular region, perturbing its anchoring and catalytic activity. The phenotype in human\n                      <jats:italic>PLXND1<\/jats:italic>\n                      mutation is closely related to that of knockout mice for\n                      <jats:italic>PLXND1<\/jats:italic>\n                      , its co\u2010receptor neuropilin\u20101 or its ligand\n                      <jats:italic>SEMA3C<\/jats:italic>\n                      . It is therefore suggested that\n                      <jats:italic>SEMA3C<\/jats:italic>\n                      signaling, propagated through the heterodimer receptor plexin\u2010D1\/neuropilin, is important for truncus arteriosus septation. Confirmation of this observation will require the identification of\n                      <jats:italic>PLXND1<\/jats:italic>\n                      mutations in additional patients. Exome analysis is valuable for molecular investigation of single patients with congenital heart defects in whom chromosomal copy number variants have been excluded. \u00a9 2013 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.36194","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T13:28:41Z","timestamp":1383053321000},"page":"3115-3120","source":"Crossref","is-referenced-by-count":38,"title":["Isolated truncus arteriosus associated with a mutation in the plexin\u2010D1 gene"],"prefix":"10.1002","volume":"161","author":[{"given":"Asaf","family":"Ta\u2010Shma","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology Hadassah, Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro Leonardo","family":"Pierri","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnology and Biopharmaceutics University of Bari Aldo Moro Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Stepensky","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah, Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avraham","family":"Shaag","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah, Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamir","family":"Zenvirt","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah, Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Elpeleg","sequence":"additional","affiliation":[{"name":"Monique and Jacques Roboh Department of Genetic Research Hadassah, Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azaria J.J.T.","family":"Rein","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Hadassah, Hebrew University Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1710"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.796698"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/521227"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23524"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1242\/dev.128.16.3061","article-title":"Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption","volume":"128","author":"Feiner L","year":"2001","journal-title":"Development"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.06.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00259-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00169-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906923106"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2012-302543"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-004-0775-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6844926"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904744106"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1740"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27363"},{"key":"e_1_2_7_17_1","first-page":"215","article-title":"Bioinformatics in protein analysis","volume":"88","author":"Persson B","year":"2000","journal-title":"EXS"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.60.1.27"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2010.04.008"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320500317"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320360322"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.5"},{"key":"e_1_2_7_23_1","first-page":"97","article-title":"Comparative protein structure modeling. 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