{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:09:02Z","timestamp":1790759342887,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Joubert syndrome (JBTS) is a rare genetic disorder that is characterized by midbrain\u2010hindbrain malformations. Multiple variants in genes that affect ciliary function contribute to the genetic and clinical heterogeneity of JBTS and its subtypes. However, the correlation between genotype and phenotype has not been elucidated due to the limited number of patients available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we observed different clinical features in two siblings from the same family. The older sibling was classified as a pure JBTS patient, whereas her younger sibling displayed oral\u2010facial\u2010digital defects and was therefore classified as an oral\u2010facial\u2010digital syndrome type VI (OFD VI) patient. Next, we performed human genetic tests to identify the potential pathogenic variants in the two siblings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic sequencing indicated that both siblings harbored compound heterozygous variants of a missense variant (c.1067C&gt;T, p.S356F) and a frameshift variant (c.8377_8378del, p.E2793Lfs*24) in <jats:italic>CPLANE1<\/jats:italic> (NM_023073.3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reports that two novel <jats:italic>CPLANE1<\/jats:italic> variants are associated with the occurrence of JBTS and OFD VI. These results help elucidate the intrafamilial phenotypic variability associated with <jats:italic>CPLANE1<\/jats:italic> variants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1682","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T10:44:40Z","timestamp":1617705880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical heterogeneity and intrafamilial variability of Joubert syndrome in two siblings with <i>CPLANE1<\/i> variants"],"prefix":"10.1002","volume":"9","author":[{"given":"Xiujuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medicine Sciences Key Laboratory of Molecular Cardiovascular Science Ministry of Education Peking University Beijing China"},{"name":"Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Department of Pathophysiology Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2797-9178","authenticated-orcid":false,"given":"Yue","family":"Shen","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Developmental Pediatrics The Second Hospital of Jilin University Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruikun","family":"Cai","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Chen","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Yu","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Cheng","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"},{"name":"Graduate School of Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology School of Basic Medicine Sciences Key Laboratory of Molecular Cardiovascular Science Ministry of Education Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1855-985X","authenticated-orcid":false,"given":"Minna","family":"Luo","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0352-6548","authenticated-orcid":false,"given":"Muqing","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Department of Pathophysiology Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongfu","family":"Cao","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7674-3589","authenticated-orcid":false,"given":"Xu","family":"Ma","sequence":"additional","affiliation":[{"name":"National Human Genetic Resources Center National Research Institute for Family Planning Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22134"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-017-0019-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37092"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2014.20"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.03.012"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.19.9.813"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.84"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jdn.10029"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1385-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.52010\/ijom.2007.33.1.5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-013-0375-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912602117"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1508-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70136-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.011"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3558"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-59565-2.00058-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2015.45"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3201"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34173"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1682","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1682","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T02:21:40Z","timestamp":1693362100000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/mgg3.1682"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1682","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]},"assertion":[{"value":"2021-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1682"}}