{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:40:32Z","timestamp":1781343632306,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Biallelic <jats:italic>CC2D2A<\/jats:italic> variants are associated with a wide range of neurodevelopmental disorders including Meckel syndrome. Here we report a Japanese girl with Meckel syndrome harboring a pathogenic deep intronic variant (NM_001378615.1:c.1149+3569A&gt;G) and an exonic LINE\u20101 insertion, which was predicted to cause aberrant splicing by SpliceAI and was detected by TEMP2 program, respectively. RNA analysis using urine\u2010derived cells (UDCs) showed retention of 149\u2010bp intronic sequences, leading to frameshift. Immunoblotting showed marked reduction of CC2D2A protein in the patient. Our report demonstrated that utilization of transposon detection tool and functional analysis using UDCs will increase diagnostic yield of genome sequencing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12507","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T08:26:23Z","timestamp":1679905583000},"page":"196-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of pathogenic deep intronic variant and exonic LINE\u20101 insertion in a patient with Meckel syndrome"],"prefix":"10.1111","volume":"87","author":[{"given":"Sachiko","family":"Miyamoto","sequence":"first","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Showa University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuko","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotomo","family":"Saitsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Hamamatsu University School of Medicine  Hamamatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1603"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/2Fejhg.2014.174"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg798"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030573"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2022.100108"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010022\u201001073\u20103"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13100\u2010016\u20100065\u20109"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010022\u201001016\u20101"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv033"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010020\u201002053\u20109"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.11.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.60"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010021\u201000594\u20105"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/life12091425"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1714458"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38167"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab010"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T07:10:46Z","timestamp":1692342646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/ahg.12507"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12507","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,27]]},"assertion":[{"value":"2022-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}