{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:59:03Z","timestamp":1781744343168,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>TMEM17<\/jats:italic>\n                    encodes a transition zone protein essential for ciliary function. Three cases with homozygous variants in\n                    <jats:italic>TMEM17<\/jats:italic>\n                    in primary ciliopathies (Joubert and Oral\u2010Facial\u2010Digital syndrome) have been reported. We investigated whether biallelic\n                    <jats:italic>TMEM17<\/jats:italic>\n                    variants contribute to primary ciliopathies. We queried our Biodatabank and evaluated the gene\u2010disease relationship (GDR) according to the ClinGen recommendations. Four unrelated patients (four families) were identified with a clinical diagnosis of Meckel\u2010Gruber syndrome (MGS) and novel homozygous variants: NM_198276.3:c.4del p.(Glu2Serfs*58); NM_198276.3:c.366dup p.(Pro123Thrfs*9); and NM_198276.3:c.368C&gt;G p.(Pro123Arg). A fifth family lost three foetuses with MGS phenotype, both parents are heterozygote carriers (NM_198276.3:c.4del p.(Glu2Serfs*58)) but biological material from the foetuses was not available. The cases in this study had a severe prenatal phenotype, including encephalocele, polycystic kidney dysplasia, and polydactyly, leading to early lethality. This study strengthens the gene\u2010disease association of\n                    <jats:italic>TMEM17<\/jats:italic>\n                    , upgrading it from \u201climited\u201d to \u201cmoderate.\u201d We expand the phenotypic spectrum, ranging from MGS\u2014with prenatal onset and early lethality\u2014to Oral\u2010Facial\u2010Digital and Joubert syndromes. Our findings indicate that loss\u2010of\u2010function variants may underlie the most severe\n                    <jats:italic>TMEM17<\/jats:italic>\n                    ciliopathy manifestations, suggesting a potential genotype\u2013phenotype correlation.\n                  <\/jats:p>","DOI":"10.1111\/cge.14767","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T03:18:02Z","timestamp":1751858282000},"page":"582-588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biallelic Variants in\n                    <i>TMEM17<\/i>\n                    Cause Meckel\u2010Gruber Syndrome Within the Ciliopathy Spectrum"],"prefix":"10.1111","volume":"108","author":[{"given":"Luba M.","family":"Pardo","sequence":"first","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-5929","authenticated-orcid":false,"given":"Javier","family":"Martini","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emir","family":"Zonic","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia S.","family":"Almeida","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Iqbal","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukunth","family":"Sadagopan","sequence":"additional","affiliation":[{"name":"CENTOGENE GmbH  Rostock 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for Health Sciences (KSAU\u2010HS), Ministry of National Guard Health Affairs (MNG\u2010HA)  Riyadh Saudi Arabia"},{"name":"Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG\u2010HA), Riyadh  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-2464","authenticated-orcid":false,"given":"Farhan Javed","family":"Dar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Laboratory Medicine and Blood Bank International Medical Center  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadwah","family":"Tahir","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Umm Al\u2010Qura University  Makkah Saudi 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Hamad","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine Imam Abdulrahman Bin Faisal University  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-5267","authenticated-orcid":false,"given":"Bader","family":"Alhaddad","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, College of Medicine Imam Abdulrahman Bin Faisal University  Dammam Saudi Arabia"},{"name":"Lifera Omics  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sondos","family":"Almubayedh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, College of Medicine Imam Abdulrahman Bin Faisal University  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama","family":"Alabdi","sequence":"additional","affiliation":[{"name":"Genomic Medicine Center of Excellence King Faisal Specialist 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H.","year":"2018"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21116"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-121321-093528"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14767","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T07:47:32Z","timestamp":1759823252000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,7]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/cge.14767"],"URL":"https:\/\/doi.org\/10.1111\/cge.14767","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14767\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14767\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14767\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14767\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14767\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14767\/v2\/response1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,7]]},"assertion":[{"value":"2025-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}