{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:08:53Z","timestamp":1790633333689,"version":"4.1.0"},"reference-count":3,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Fetal phenotype<\/jats:title><jats:p>A couple of Ashkenazi Jewish descent was referred for an early anatomy scan at 14\u00a0+\u00a02\u00a0weeks of gestation following a previous pregnancy termination due to posterior encephalocele and enlarged kidneys. The index pregnancy was also positive for several fetal abnormalities, including enlarged kidneys with cystic dysplasia and abnormal cerebellar morphology highly suggestive of Joubert syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Genetic diagnostic test performed, result, and interpretation<\/jats:title><jats:p>Trio exome sequencing revealed compound heterozygosity for variants in the <jats:italic>TMEM67<\/jats:italic> gene: a known pathogenic maternally inherited variant found in <jats:italic>trans<\/jats:italic> with a paternal intronic variant of unknown significance. RNA analysis revealed that the intronic variant creates a cryptic acceptor splice site in intron 12, leading to the insertion of 22 bp and causing a frameshift with a premature stop codon. This analysis enabled the reclassification of the intronic variant to <jats:italic>likely pathogenic<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Implications and novelty<\/jats:title><jats:p>This information empowered the couple to make informed reproductive choices and opt for preimplantation genetic testing (PGT) for future pregnancies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6248","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T03:29:24Z","timestamp":1665545364000},"page":"1484-1487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Upgrading an intronic <i>TMEM67<\/i> variant of unknown significance to likely pathogenic through RNA studies and community data sharing"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-3621","authenticated-orcid":false,"given":"Alina","family":"Kurolap","sequence":"first","affiliation":[{"name":"The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Mory","sequence":"additional","affiliation":[{"name":"The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Simchoni","sequence":"additional","affiliation":[{"name":"The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9868-3548","authenticated-orcid":false,"given":"Karina","family":"Krajden Haratz","sequence":"additional","affiliation":[{"name":"Division of Ultrasound in Obstetrics and Gynecology Lis Maternity and Hospital for Women's Health Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0864-206X","authenticated-orcid":false,"given":"Gustavo","family":"Malinger","sequence":"additional","affiliation":[{"name":"Division of Ultrasound in Obstetrics and Gynecology Lis Maternity and Hospital for Women's Health Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1073-6348","authenticated-orcid":false,"given":"Roee","family":"Birnbaum","sequence":"additional","affiliation":[{"name":"Division of Ultrasound in Obstetrics and Gynecology Lis Maternity and Hospital for Women's Health Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Baris Feldman","sequence":"additional","affiliation":[{"name":"The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8622-7668","authenticated-orcid":false,"given":"Yuval","family":"Yaron","sequence":"additional","affiliation":[{"name":"The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center  Tel Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.24885"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12071078"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6248","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pd.6248","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6248","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T02:11:30Z","timestamp":1692670290000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,21]]},"references-count":3,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/pd.6248"],"URL":"https:\/\/doi.org\/10.1002\/pd.6248","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,21]]},"assertion":[{"value":"2022-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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