{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:15Z","timestamp":1753869735774,"version":"3.41.2"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC1005303"],"award-info":[{"award-number":["2021YFC1005303"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Short\u2010rib thoracic dysplasia (SRTD) and Joubert syndrome (JS) are rare genetic ciliopathies, and individuals with either syndrome can manifest cerebellar malformation and variable developmental delays. However, neither of these conditions is easily diagnosed during pregnancy due to a limited fetal phenotype. Here, we investigated a fetus that was initially observed to have short limbs and polydactyly and discovered a compound heterozygous pathogenesis through exome sequencing (ES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Simultaneous trio\u2010ES and chromosome microarray analysis was provided for the fetus. The presence and effects of these variants on splicing were further validated at the DNA and RNA levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Only short limbs and post\u2010axial polydactyly of the fetus were detected during the second trimester. Two variants (c.3940+1G&gt;A and c.3303G&gt;A), affecting splicing of <jats:italic>KIAA0586,<\/jats:italic> were identified from amniocytes through ES and validated by Sanger sequencing. More intensive fetal monitoring was applied, and the fetus was also found to have deformed cerebellar malformation and a constricted thoracic cage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Herein, we report the genetic pathogenesis of SRTD and\/or JS associated with <jats:italic>KIAA0586<\/jats:italic> in a fetus. The novel splicing variants observed expand the spectrum of <jats:italic>KIAA0586<\/jats:italic> in SRTD and\/or JS. Based on the genetic data and the distinct corresponding phenotypes discovered by imaging examination, a comprehensive diagnosis was made during pregnancy and more valuable prognostic information was provided for the parents.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2124","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T15:48:29Z","timestamp":1671551309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Compound heterozygous splicing variants in <scp><i>KIAA0586<\/i><\/scp> cause fetal short\u2010rib thoracic dysplasia and cerebellar malformation: Use of exome sequencing in prenatal diagnosis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-4827","authenticated-orcid":false,"given":"Qianying","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bocheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinqin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"},{"name":"Department of Ultrasound West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyi","family":"Wen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"},{"name":"Department of Radiology West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6200-5865","authenticated-orcid":false,"given":"Mei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology West China Second University Hospital, Sichuan University  Chengdu China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23626"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.06.003"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103087"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22821"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-20"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2012.01.020"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2012.04.018"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.976"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5550"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31940-8"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0731-7"},{"key":"e_1_2_11_13_1","unstructured":"Parisi M. A. &Glass I.(2003).Joubert syndrome and related disorders.http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1325\/"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32042-7"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.11.003"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.142"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.148"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00215"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jum.14215"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2124","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.2124","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T02:45:38Z","timestamp":1692585938000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1002\/mgg3.2124"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2124","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"assertion":[{"value":"2022-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2124"}}