{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:08:32Z","timestamp":1793362112506,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T00:00:00Z","timestamp":1424217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["DE017953"],"award-info":[{"award-number":["DE017953"]}]},{"name":"NIH","award":["TR000445"],"award-info":[{"award-number":["TR000445"]}]},{"name":"NIH","award":["DE021071-01"],"award-info":[{"award-number":["DE021071-01"]}]},{"name":"NIH","award":["DE08559"],"award-info":[{"award-number":["DE08559"]}]},{"name":"NIH","award":["DE20057"],"award-info":[{"award-number":["DE20057"]}]},{"name":"NIH","award":["T32-GM008629"],"award-info":[{"award-number":["T32-GM008629"]}]},{"name":"NIH","award":["T15-LM007059"],"award-info":[{"award-number":["T15-LM007059"]}]},{"name":"The Jean Renny Endowment for Craniofacial Research","award":["G0901539"],"award-info":[{"award-number":["G0901539"]}]},{"name":"The Healing Foundation"},{"name":"The Wellcome Trust Institutional Strategic Support Fund","award":["097820"],"award-info":[{"award-number":["097820"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and\/or palate, syndactyly, and genital malformations. Heterozygous mutations in\n                      <jats:italic>IRF6<\/jats:italic>\n                      cause popliteal pterygium syndrome (PPS) while homozygous mutations in\n                      <jats:italic>RIPK4<\/jats:italic>\n                      or\n                      <jats:italic>CHUK (IKKA)<\/jats:italic>\n                      cause the more severe Bartsocas\u2013Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study, we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of\n                      <jats:italic>IRF6<\/jats:italic>\n                      and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in\n                      <jats:italic>RIPK4<\/jats:italic>\n                      can cause features with a range of severity along the PPS\u2010BPS spectrum and that mutations in\n                      <jats:italic>IKKA<\/jats:italic>\n                      can cause a range of features along the BPS\u2010Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate\n                      <jats:italic>IRF6<\/jats:italic>\n                      ,\n                      <jats:italic>RIPK4<\/jats:italic>\n                      , and\n                      <jats:italic>CHUK<\/jats:italic>\n                      (\n                      <jats:italic>IKKA<\/jats:italic>\n                      ) in potentially interconnected pathways governing epidermal and craniofacial development. \u00a9 2015 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.36896","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T01:39:36Z","timestamp":1424223576000},"page":"545-552","source":"Crossref","is-referenced-by-count":49,"title":["Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders"],"prefix":"10.1002","volume":"167","author":[{"given":"Elizabeth J.","family":"Leslie","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Dental School Manchester Academic Health Sciences Centre University of Manchester Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Washington and Seattle Children's Craniofacial Center Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankur","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Institute of Medical Sciences Banaras Hindu University India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Goudy","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Vanderbilt University Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faroug","family":"Ababneh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics King Abdul Aziz Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamia","family":"Alsubaie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics King Abdul Aziz Medical City Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaik\u2010Siew","family":"Ch'ng","sequence":"additional","affiliation":[{"name":"Department of Genetics Kuala Lumpur Hospital Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M. B. H.","family":"van der Laar","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Jeannette","family":"M. Hoogeboom","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Dunnwald","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Maulana Azad Medical College Lok Nayak Hospital New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawina","family":"Jiramongkolchai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Vanderbilt University Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Standley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Robert","family":"Manak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"},{"name":"Department of Biology University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Dental School Manchester Academic Health Sciences Centre University of Manchester Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503523200"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.3577405"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e318197a49a"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2933"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201619"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35913"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.8.1373"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01075-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1903"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.014"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng985"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0911698"},{"key":"e_1_2_6_14_1","first-page":"888","article-title":"Popliteal pterygium syndrome: A clinical study of three families and report of linkage to the Van der Woude syndrome locus on 1q32","volume":"36","author":"Lees MM","year":"1999","journal-title":"J Med Genet"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36133"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.141"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8166-3-8"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33338"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks389"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.013"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40267"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1894"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<452::AID-BIES7>3.0.CO;2-K"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2009.223"},{"key":"e_1_2_6_25_1","volume-title":"IRF6\u2010Related Disorders","author":"Schutte BC","year":"1993"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30096"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40266"},{"key":"e_1_2_6_28_1","first-page":"269","article-title":"Bartsocas\u2010Papas Syndrome with Variable Expressivity in an Egyptian Family","volume":"23","author":"Zaki MS","year":"2012","journal-title":"Genetic Counseling"}],"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.36896","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36896","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36896","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T14:48:32Z","timestamp":1696603712000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,18]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/ajmg.a.36896"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36896","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,18]]}}}