{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T01:50:05Z","timestamp":1775958605534,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["19YF1452200"],"award-info":[{"award-number":["19YF1452200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Joubert syndrome (JS) is a genetically heterogeneous disorder; its genetic etiology involves more than 35 genes, and a limited number of studies have investigated the pathogenic mechanism of variants in patients with JS. RNA splicing analysis is critical to determine the functional significance for noncanonical splicing variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing was performed to screen the causative gene variants in a JS family. Sanger sequencing was used to verify the variants. cDNA PCR products were analyzed and functional experiments were performed to determine the pathogenicity of the variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The clinical phenotypes and <jats:italic>CPLANE1<\/jats:italic> variants in the JS patient were analyzed and proved consistent. We identified two novel heterozygous variants of <jats:italic>CPLANE1<\/jats:italic> in the proband first, including c.4459del (frameshift variant) and c.7534\u201014G\u00a0&gt;\u00a0A (intronic variant). We analyzed the pathogenic consequences of the 2 variants and classified the c.4459del as likely pathogenic according to the ACMG\/AMP guidelines; however, the pathogenic significance of c.7534\u201014G\u00a0&gt;\u00a0A was uncertain. Furthermore, we performed RNA splicing analysis and revealed that the noncanonical splicing variant (c.7534\u201014G\u00a0&gt;\u00a0A) caused aberrant exon 37 skipping. It produced an aberrant transcript that was predicted to encode a C\u2010terminal truncated protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The genetic variation spectrum of JS caused by <jats:italic>CPLANE1<\/jats:italic> was updated. Two novel variants further deepened our insight into the disease's molecular mechanism and confirmed the significance of diagnostic whole\u2010exome sequencing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1877","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T11:00:02Z","timestamp":1643454002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exome sequencing and <scp>RNA<\/scp> analysis identify two novel <scp><i>CPLANE1<\/i><\/scp> variants causing Joubert syndrome"],"prefix":"10.1002","volume":"10","author":[{"given":"Hongjun","family":"Fei","sequence":"first","affiliation":[{"name":"Department of Reproductive Genetics International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Genetics International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Genetics International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-6670","authenticated-orcid":false,"given":"Junyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Genetics International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22134"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103087"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5109"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001951"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.015588"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.159"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25491"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw010"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-017-0399-2"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0273-4"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.84"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jdn.10029"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901400605"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39796-w"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3233\/TRD-190041"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201648"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013808"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.01.012"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1508-3"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.011"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3536495"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.86"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.204"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0000000000000950"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphg.98"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104212"}],"container-title":["Molecular Genetics &amp; 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