{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:13Z","timestamp":1772160073674,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W01761X\/1"],"award-info":[{"award-number":["MR\/W01761X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203141\/Z\/16\/Z"],"award-info":[{"award-number":["203141\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>PKDCC<\/jats:italic>\n                    encodes a component of Hedgehog signalling required for normal chondrogenesis and skeletal development. Although biallelic\n                    <jats:italic>PKDCC<\/jats:italic>\n                    variants have been implicated in rhizomelic shortening of limbs with variable dysmorphic features, this association was based on just two patients. In this study, data from the 100\u2009000 Genomes Project was used in conjunction with exome sequencing and panel\u2010testing results accessed via international collaboration to assemble a cohort of eight individuals from seven independent families with biallelic\n                    <jats:italic>PKDCC<\/jats:italic>\n                    variants. The allelic series included six frameshifts, a previously described splice\u2010donor site variant and a likely pathogenic missense variant observed in two families that was supported by in silico structural modelling. Database queries suggested that the prevalence of this condition is between 1 of 127 and 1 of 721 in clinical cohorts with skeletal dysplasia of unknown aetiology. Clinical assessments, combined with data from previously published cases, indicate a predominantly upper limb involvement. Micrognathia, hypertelorism and hearing loss appear to be commonly co\u2010occurring features. In conclusion, this study strengthens the link between biallelic inactivation of\n                    <jats:italic>PKDCC<\/jats:italic>\n                    and rhizomelic limb\u2010shortening and will enable clinical testing laboratories to better interpret variants in this gene.\n                  <\/jats:p>","DOI":"10.1111\/cge.14324","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T04:25:07Z","timestamp":1678422307000},"page":"121-126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The prevalence and phenotypic range associated with biallelic\n                    <scp>\n                      <i>PKDCC<\/i>\n                    <\/scp>\n                    variants"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7334-0602","authenticated-orcid":false,"given":"Alistair T.","family":"Pagnamenta","sequence":"first","affiliation":[{"name":"NIHR Biomedical Research Centre, Wellcome Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca S.","family":"Belles","sequence":"additional","affiliation":[{"name":"Geisinger Health System  Danville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonnie Anne","family":"Salbert","sequence":"additional","affiliation":[{"name":"Geisinger Health System  Danville Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid M.","family":"Wentzensen","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"Guillen Sacoto","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis Jeshira Reynoso","family":"Santos","sequence":"additional","affiliation":[{"name":"Joe DiMaggio Children's Hospital  Hollywood Florida USA"},{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alesky","family":"Caffo","sequence":"additional","affiliation":[{"name":"Joe DiMaggio Children's Hospital  Hollywood Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Ferla","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre, Wellcome Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benito","family":"Banos\u2010Pinero","sequence":"additional","affiliation":[{"name":"Oxford Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, The Churchill Hospital  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Pawliczak","sequence":"additional","affiliation":[{"name":"South East Genomic Laboratory Hub Guy's Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Makvand","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology &amp; Genetics Center  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-7778","authenticated-orcid":false,"given":"Hossein","family":"Najmabadi","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology &amp; Genetics Center  Tehran Iran"},{"name":"Genetics Research Center University of Social Welfare &amp; Rehabilitation Science  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Genomics England Research Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases UCL Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Lester","sequence":"additional","affiliation":[{"name":"Oxford Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, The Churchill Hospital  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-9239","authenticated-orcid":false,"given":"Ana Lucia","family":"Yanez\u2010Felix","sequence":"additional","affiliation":[{"name":"Human Genetics Department National Pediatrics Institute  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilo E.","family":"Villarroel\u2010Cortes","sequence":"additional","affiliation":[{"name":"Human Genetics Department National Pediatrics Institute  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Xia","sequence":"additional","affiliation":[{"name":"Baylor Genetics  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khowla","family":"Al Fayez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Clinical Genetic and Metabolic Medicine Prince Sultan Medical Military City  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal","family":"Al Hashem","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Clinical Genetic and Metabolic Medicine Prince Sultan Medical Military City  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Shears","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Foundation Trust  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melita","family":"Irving","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaka C.","family":"Offiah","sequence":"additional","affiliation":[{"name":"Department of Oncology &amp; Metabolism University of Sheffield  Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-4728","authenticated-orcid":false,"given":"Ariana","family":"Kariminejad","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology &amp; Genetics Center  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre, Wellcome Centre for Human Genetics University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.84"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20190784"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2013.03.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21822"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102018\u2010105639"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035790"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.06.013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.14601"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.1989.tb02912.x"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14324","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14324","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T14:10:02Z","timestamp":1692454202000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/cge.14324"],"URL":"https:\/\/doi.org\/10.1111\/cge.14324","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14324\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14324\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14324\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14324\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14324\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]},"assertion":[{"value":"2022-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}