{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:52:00Z","timestamp":1791456720925,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR\u2010MR1\u20102023\u201012377314"],"award-info":[{"award-number":["PNRR\u2010MR1\u20102023\u201012377314"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Biallelic pathogenic variants in\n                    <jats:italic>TTC21B,<\/jats:italic>\n                    encoding the retrograde intraflagellar transport protein IFT139, are a known cause of renal and skeletal ciliopathies. Single heterozygous variants in this gene were found to be enriched in a cohort of patients with various ciliopathy phenotypes, including three individuals with Joubert syndrome (JS), a neurodevelopmental ciliopathy characterized by a peculiar cerebellar and brainstem malformation. It was then suggested that\n                    <jats:italic>TTC21B<\/jats:italic>\n                    could act as a modifier gene for ciliopathies. Here we report a patient homozygous for the hypomorphic founder variant p.Pro209Leu in\n                    <jats:italic>TTC21B<\/jats:italic>\n                    , who presented typical neurological and neuroradiological features of JS, along with mild renal dysplasia and retinal dystrophy. To our knowledge, this is the first case reported with molecularly confirmed JS caused by biallelic pathogenic variants in\n                    <jats:italic>TTC21B,<\/jats:italic>\n                    expanding the spectrum of\n                    <jats:italic>TTC21B<\/jats:italic>\n                    \u2010associated ciliopathies, further highlighting the complex genetic basis of ciliopathies.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70319","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:09:16Z","timestamp":1791454156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>TTC21B<\/i>\n                    <\/scp>\n                    : From Modifier to Causative Gene in Joubert Syndrome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-0066","authenticated-orcid":false,"given":"Valentina","family":"Serpieri","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-665X","authenticated-orcid":false,"given":"Fulvio","family":"D'Abrusco","sequence":"additional","affiliation":[{"name":"Neurogenetics Research Centre, IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-4088","authenticated-orcid":false,"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"Neuroradiology Department Advanced Imaging and Radiomics Center, IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1475-938X","authenticated-orcid":false,"given":"Thouraya","family":"Ben Younes","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, LR18SP04 National Institute Mongi Ben Hmida of Neurology  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-5662","authenticated-orcid":false,"given":"Ichraf","family":"Kraoua","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, LR18SP04 National Institute Mongi Ben Hmida of Neurology  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0600-6820","authenticated-orcid":false,"given":"Enza Maria","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Pavia  Pavia Italy"},{"name":"Neurogenetics Research Centre, IRCCS Mondino Foundation  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100039\u20101700804"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102015\u2010103087"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10633\u2010024\u201009996\u20105"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13816810.2021.1888131"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv453"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg\u20102025\u2010110987"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.756"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.795216"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31963"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010021\u201000925\u2010x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.4266\u201019"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1010172"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101126"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12550"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31964"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.082552"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010024\u201001880\u20100"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.60"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102012\u2010101284"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(25)00226\u20101"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62093"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1891\/NN\u20102024\u20100052"},{"key":"e_1_2_9_24_1","first-page":"1879","volume-title":"Handbook of Clinical Neurology","author":"Valente E. M.","year":"2013"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467\u2010010\u20101731\u20107"}],"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.70319","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70319","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:09:17Z","timestamp":1791454157000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":24,"alternative-id":["10.1002\/ajmg.a.70319"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70319","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2026-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70319"}}