{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T23:30:26Z","timestamp":1773790226614,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"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":[[2017,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Tricho\u2013Rhino\u2013Phalangeal syndrome is a rare autosomal dominant genetic disorder caused by mutations in the <jats:italic>TRPS1<\/jats:italic> gene. This malformation syndrome is characterized by distinctive craniofacial features including sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone\u2010shaped epiphyses at the phalanges, hip malformations, and short stature. In this report, we describe two patients with the physical manifestations and genotype of TRPS type I but with learning\/intellectual disability not typically described as part of the syndrome. The first patient has a novel heterozygous two\u2010base\u2010pair deletion of nucleotides at 3198\u20103199 (c.3198\u20103199delAT) in the <jats:italic>TRPS1<\/jats:italic> gene causing a translational frameshift and subsequent alternate stop codon. The second patient has a 3.08 million base\u2010pair interstitial deletion at 8q23.3 (113,735,487\u2013116,818,578), which includes the <jats:italic>TRPS1<\/jats:italic> gene and <jats:italic>CSMD3<\/jats:italic>. Our patients have characteristic craniofacial features, Legg\u2013Perthes syndrome, various skeletal abnormalities including cone shaped epiphyses, anxiety (first patient), and intellectual disability, presenting unusual phenotypes that add to the clinical spectrum of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38204","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T05:06:46Z","timestamp":1488517606000},"page":"1663-1667","source":"Crossref","is-referenced-by-count":8,"title":["Two cases of Legg\u2013Perthes and intellectual disability in Tricho\u2013Rhino\u2013Phalangeal syndrome type 1 associated with novel <i>TRPS1<\/i> mutations"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-397X","authenticated-orcid":false,"given":"Jordana L.","family":"Gilman","sequence":"first","affiliation":[{"name":"Section of Medical Genetics SUNY Upstate Medical University Syracuse New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather A.","family":"Newman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California Irvine, Orange California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California Irvine, Orange California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn E.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California Irvine, Orange California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L.","family":"Puckett","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California Irvine, Orange California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David K.","family":"Morohashi","sequence":"additional","affiliation":[{"name":"Division of Family Medicine, School of Medicine University of California Irvine California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constance","family":"Stein","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics SUNY Upstate Medical University Syracuse New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Palomino","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery SUNY Upstate Medical University Syracuse New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert Roger","family":"Lebel","sequence":"additional","affiliation":[{"name":"Section of Medical Genetics SUNY Upstate Medical University Syracuse New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia E.","family":"Kimonis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic and Genomic Medicine University of California Irvine, Orange California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-9668.101936"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-199505000-00023"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00442088"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00024.x"},{"issue":"5","key":"e_1_2_6_8_1","first-page":"475","article-title":"Tricho\u2010rhino\u2010phalangeal syndrome","volume":"21","author":"Giedion A.","year":"1966","journal-title":"Helvetica Paediatrica Acta"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2007.06.005"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380200010"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.1.31"},{"issue":"1","key":"e_1_2_6_13_1","first-page":"81","article-title":"Genotypic and phenotypic spectrum in tricho\u2010rhino\u2010phalangeal syndrome types I and III","volume":"68","author":"L\u00fcdecke H. J.","year":"2001","journal-title":"American Journal of Medical Genetics"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.03.002"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1993.tb12676.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2016.03.003"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/71717"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08158.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e32834e9248"}],"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.38204","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T11:11:06Z","timestamp":1696590666000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,3]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1002\/ajmg.a.38204"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38204","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,3]]}}}