{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:48:58Z","timestamp":1792986538481,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T00:00:00Z","timestamp":1516752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,3]]},"abstract":"\n Ellis\u2010van Creveld syndrome (\n EvC<\/jats:styled-content>\n ) is a chondral and ectodermal dysplasia caused by biallelic mutations in the\n \n EVC<\/jats:styled-content>\n <\/jats:italic>\n ,\n \n EVC2<\/jats:styled-content>\n <\/jats:italic>\n and\n \n WDR35<\/jats:styled-content>\n <\/jats:italic>\n genes. A proportion of cases with clinical diagnosis of\n EvC<\/jats:styled-content>\n , however, do not carry mutations in these genes. To identify the genetic cause of\n EvC<\/jats:styled-content>\n in a cohort of mutation\u2010negative patients, exome sequencing was undertaken in a family with 3 affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting\/overlapping\n EvC<\/jats:styled-content>\n . Compound heterozygosity for the c.\n 2T<\/jats:styled-content>\n >C (p.Met1?) and c.\n 662C<\/jats:styled-content>\n >T (p.\n Thr221Ile<\/jats:styled-content>\n ) variants in\n \n DYNC2LI1<\/jats:styled-content>\n <\/jats:italic>\n , which encodes a component of the intraflagellar transport\u2010related dynein\u20102 complex previously found mutated in other short\u2010rib thoracic dysplasias, was identified in the 3 affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a truncating change (p.Val141*) in 2 siblings with\n EvC<\/jats:styled-content>\n from a second family, while a newborn with a more severe phenotype carried 2\n \n DYNC2LI1<\/jats:styled-content>\n <\/jats:italic>\n truncating variants. Our findings indicate that\n \n DYNC2LI1<\/jats:styled-content>\n <\/jats:italic>\n mutations are associated with a wider clinical spectrum than previously appreciated, including\n EvC<\/jats:styled-content>\n , with the severity of the phenotype likely depending on the extent of defective\n DYNC2LI1<\/jats:styled-content>\n function.\n <\/jats:p>","DOI":"10.1111\/cge.13128","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T07:43:11Z","timestamp":1504165391000},"page":"632-639","source":"Crossref","is-referenced-by-count":32,"title":["Biallelic mutations in\n \n DYNC2LI1<\/scp>\n <\/i>\n are a rare cause of Ellis\u2010van Creveld syndrome"],"prefix":"10.1111","volume":"93","author":[{"given":"M.","family":"Niceta","sequence":"first","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Margiotti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Policlinico Umberto 1, Universit\u00e0 \u201cSapienza\u201d Rome Italy"},{"name":"Molecular Genetics Unit Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.C.","family":"Digilio","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Guida","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bruselles","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine Istituto Superiore di Sanit\u00e0 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Pizzi","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ferraris","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Memo","sequence":"additional","affiliation":[{"name":"Pediatric Unit Ospedale San Martino Belluno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Laforgia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Human Oncology Universit\u00e0 di Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9505-5906","authenticated-orcid":false,"given":"M.L.","family":"Dentici","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Consoli","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Torrente","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.L.","family":"Ruiz\u2010Perez","sequence":"additional","affiliation":[{"name":"Department of Experimental Models of Human Diseases Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d, CSIC\u2010UAM Madrid Spain"},{"name":"CIBER de enfermedades Raras (CIBERER) ISCIII Val\u00e8ncia Spain"},{"name":"Instituto de Gen\u00e9tica M\u00e9dica y Molecular (INGEMM) Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Dallapiccola","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Universit\u00e0 \u201cSapienza\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"De Luca","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9672","authenticated-orcid":false,"given":"M.","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.15.82.65"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-27"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990604)84:4<350::AID-AJMG8>3.0.CO;2-E"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-011-0006-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/73508"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00178-6"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/368063"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds409"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-9-14"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ajmg.c.30226","article-title":"Ellis\u2010van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia\u2010mediated diminished response to Hedgehog ligands","volume":"151","author":"Ruiz\u2010Perez VL","year":"2009","journal-title":"Am J Med Genet"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.11.005"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv152"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3282"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.03.001"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.003"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.006"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22376"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu733"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"11649","DOI":"10.1038\/srep11649","article-title":"DYNC2LI1 mutations broaden the clinical spectrum of dynein\u20102 defects","volume":"1","author":"Kessler K","year":"2015","journal-title":"Sci Rep"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20237"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02595"},{"key":"e_1_2_6_25_1","first-page":"49","article-title":"Clinical genetics and pathobiology of ciliary chondrodysplasias","volume":"3","author":"Schmidts M","year":"2014","journal-title":"J Pediatr Genet"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"7092","DOI":"10.1038\/ncomms8092","article-title":"Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome","volume":"16","author":"Taylor SP","year":"2015","journal-title":"Nat Commun"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.015"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.10.007"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T13:18:47Z","timestamp":1695647927000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,24]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/cge.13128"],"URL":"https:\/\/doi.org\/10.1111\/cge.13128","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,24]]}}}