{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:27:28Z","timestamp":1786976848797,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T00:00:00Z","timestamp":1510444800000},"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":[[2018,1]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Individuals with\n                      <jats:italic>Tumor Protein P63<\/jats:italic>\n                      (\n                      <jats:italic>TP63<\/jats:italic>\n                      )\u2010related disorders are known to present with a range of phenotypic features, including ectrodactyly, ectodermal dysplasia, cleft lip\/palate, Rapp\u2010Hodgkin, Hay\u2013Wells, and limb\u2010mammary syndromes. We present six individuals from three families, including a set of monozygotic twins, with pathogenic\n                      <jats:italic>TP63<\/jats:italic>\n                      variants who had novel clinical findings. The twins were discordant for cleft lip and palate, and the type of hand malformations, but concordant for choanal atresia, and bilateral volar nail. Both failed newborn screening for severe combined immunodeficiency (SCID) due to T\u2010cell lymphopenia. The second family included three family members across two generations. Two of these three family members had orofacial clefting, but the remaining child had a laryngeal web and hydrocele with no clefting or hand anomalies, highlighting the variable expressivity in\n                      <jats:italic>TP63<\/jats:italic>\n                      \u2010related disorders. The individual from the third family had unilateral cleft lip and palate, hydronephrosis, and bilateral volar nails. Together, these cases illustrate that: there is significant familial variability, including discordant major but concordant minor anomalies in the first ever reported set of molecularly confirmed monozygotic twins with pathogenic variants in\n                      <jats:italic>TP63<\/jats:italic>\n                      ; pathogenic variants in\n                      <jats:italic>TP63<\/jats:italic>\n                      should be considered in individuals with volar nail, which was previously only strongly associated with 4q34 deletion syndrome; and failed SCID newborn screening due to abnormal immune functioning may be part of the phenotypic spectrum of\n                      <jats:italic>TP63<\/jats:italic>\n                      \u2010related disorders, as it was reported in one prior individual and two of the individuals in our case series.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.38516","type":"journal-article","created":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T07:42:54Z","timestamp":1510472574000},"page":"75-81","source":"Crossref","is-referenced-by-count":17,"title":["Expanding the phenotypic spectrum of\n                    <i>TP63<\/i>\n                    \u2010related disorders including the first set of monozygotic twins"],"prefix":"10.1002","volume":"176","author":[{"given":"Tara","family":"Wenger","sequence":"first","affiliation":[{"name":"Division of Craniofacial Medicine Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret H.","family":"Harr","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-6149","authenticated-orcid":false,"given":"Wen\u2010Hann","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zornitza","family":"Stark","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Service Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-3507","authenticated-orcid":false,"given":"Elizabeth J.","family":"Bhoj","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2011.65"},{"issue":"11","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1002\/ajmg.a.37276","article-title":"Menkes disease with discordant phenotype in female monozygotic twins","volume":"167","author":"Burgemeister A. L.","year":"2015","journal-title":"American Journal Of Medical Genetics Part A"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37791"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81646-3"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32836"},{"issue":"1","key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1136\/jmg.40.1.55","article-title":"P63 mutations are not a major cause of non\u2010syndromic split hand\/foot malformation","volume":"40","author":"de Mollerat X. J.","year":"2003","journal-title":"Journal of Medical Genetics"},{"issue":"6","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1002\/ajmg.a.35885","article-title":"Novel mutation in TP63 associated with ectrodactyly ectodermal dysplasia and clefting syndrome and T cell lymphopenia","volume":"161","author":"Giampietro P. F.","year":"2013","journal-title":"American Journal Of Medical Genetics Part A"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/302972"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34356"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200101000-00006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000045"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32793"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcd.0000203632.86190.64"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1159\/000444852","article-title":"Generalized arterial calcification in a recipient twin: Discordant fetal hemodynamics result in differing phenotypes in monozygotic twins with an ABCC6 mutation","volume":"41","author":"Votava\u2010Smith J. K.","year":"2017","journal-title":"Fetal Diagnosis And Therapy"},{"issue":"1","key":"e_1_2_6_16_1","first-page":"347","article-title":"SmithMagenis syndrome in monozygotic twin fetuses presenting with discordant phenotypes and uteroplacental insufficiency","volume":"13","author":"Zhou Y.","year":"2016","journal-title":"Molecular Medicine Reports"}],"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.38516","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T06:45:56Z","timestamp":1695969956000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,12]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1002\/ajmg.a.38516"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38516","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,12]]}}}