{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:24:33Z","timestamp":1791494673946,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>TTC21B<\/jats:italic> encodes the protein IFT139, a critical component of the retrograde transport system within the primary cilium. Biallelic, pathogenic <jats:italic>TTC21B<\/jats:italic> variants are associated with classic ciliopathy syndromes, including nephronophthisis, Jeune asphyxiating thoracic dystrophy, and Joubert Syndrome, with ciliopathy\u2010spectrum traits such as biliary dysgenesis, primary ciliary dyskinesia, and situs inversus, and also with focal segmental glomerulosclerosis. We report a 9\u2010year\u2010old male with focal segmental glomerulosclerosis requiring kidney transplant, primary ciliary dyskinesia, and biliary dysgenesis, found by research\u2010based exome sequencing to have biallelic pathogenic <jats:italic>TTC21B<\/jats:italic> variants. A sibling with isolated heterotaxy was found to harbor the same variants. This case highlights the phenotypic spectrum and unpredictable manifestations of <jats:italic>TTC21B<\/jats:italic>\u2010related disease, and also reports the first association between <jats:italic>TTC21B<\/jats:italic> and heterotaxy, nominating <jats:italic>TTC21B<\/jats:italic> as an important new heterotaxy gene.<\/jats:p>","DOI":"10.1002\/ajmg.a.62093","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T17:29:55Z","timestamp":1612805395000},"page":"1266-1269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel heterotaxy gene: Expansion of the phenotype of <scp><i>TTC21B<\/i>\u2010spectrum<\/scp> disease"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-244X","authenticated-orcid":false,"given":"Alanna","family":"Strong","sequence":"first","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Mentch","sequence":"additional","affiliation":[{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-7461","authenticated-orcid":false,"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"The Center for Applied Genomics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Pulmonary Medicine Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.7.080505.115610"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-200405000-00005"},{"key":"e_1_2_6_4_1","unstructured":"Cowan J. R.(2015).The genetics of heterotaxy syndrome(dissertation). University of Cincinnati Cincinnati. Retrieved fromhttps:\/\/etd.ohiolink.edu\/apexprod\/rws_etd\/send_file\/send?accession=ucin1447689122&disposition=inline"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0406"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.756"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.162776"},{"key":"e_1_2_6_8_1","article-title":"Role of cilia in the pathogenesis of congenital heart disease","author":"Gabriel G. C.","year":"2020","journal-title":"Seminars in Cell & Developmental Biology"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101126"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14269"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24132"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2019.05.003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1099-5"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951114000912"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028282"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.105"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0209-6"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/nep.13008"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23362"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62093","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62093","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T09:41:44Z","timestamp":1693215704000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/ajmg.a.62093"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62093","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]},"assertion":[{"value":"2020-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}