{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T04:37:31Z","timestamp":1740112651292,"version":"3.37.3"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T00:00:00Z","timestamp":1518393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81361128006","81570568","81570468"],"award-info":[{"award-number":["81361128006","81570568","81570468"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to analyze the pathogenicity of rare\/novel synonymous or intronic variants identified in <jats:italic>ABCB11<\/jats:italic> heterozygotes presenting as progressive intrahepatic cholestasis with low \u03b3\u2010glutamyltransferase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The enrolled variants were identified in <jats:italic>ABCB11<\/jats:italic> between October 2009 and June 2016. The effects on pre\u2010RNA splicing were analyzed by <jats:italic>in silico<\/jats:italic> tools and minigene splicing assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were three intronic (c.908\u2009+\u20095G\u2009&gt;\u2009A, c.2815\u20108A\u2009&gt;\u2009G, and c.612\u201015_\u20106del10bp) and two synonymous (c.1809G\u2009&gt;\u2009A, p.K603\u00a0K and c.2418C\u2009&gt;\u2009T, p.G806G) variants with unknown significance identified in <jats:italic>ABCB11<\/jats:italic> of five <jats:italic>ABCB11<\/jats:italic> heterozygotes. Parental studies were carried out for four patients, and revealed that the variants with unknown significance were compound heterozygous with other pathogenic variants. The five variants with unknown significance had minor allele frequency &lt;0.1% or were absent from controls, and had positive prediction results by <jats:italic>in silico<\/jats:italic> tools. The effects on pre\u2010RNA splicing were further confirmed by minigene splicing assay. c.908\u2009+\u20095A caused abnormal splicing in at least 78.5\u2009\u00b1\u20093.8% of products using a cryptic splice site (ss) 22\u00a0nucleotides (nt) upstream of the wild\u2010type (WT) 5\u2032ss. Seven nucleotides of intron 22 upstream of the WT 3'ss was retained for all products from c.2815\u20108G. c.612\u201015_\u20106del caused exon 8 skipping in 24.8\u2009\u00b1\u20097.7% of products, and 55\u00a0nt of exon 8 downstream of the WT 3\u2032ss removal in remaining products. c.1809A led to exon 15 skipping. c.2418\u00a0T removed exon 20 and 62\u00a0nt of exon 21 downstream of the WT 3\u2032ss by using a cryptic ss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We successfully identified five pathogenic synonymous or intronic variants with some common features. These features might help to choose the right variant for further functional assay.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13055","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T13:13:07Z","timestamp":1515589987000},"page":"574-584","source":"Crossref","is-referenced-by-count":4,"title":["Splicing analysis of rare\/novel synonymous or intronic variants identified in <i>ABCB11<\/i> heterozygotes presenting as progressive intrahepatic cholestasis with low \u03b3\u2010glutamyltransferase"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-9873","authenticated-orcid":false,"given":"Neng\u2010Li","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital of Fudan University  Shanghai China"},{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Ling","family":"Qiu","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Cai","family":"Guan","sequence":"additional","affiliation":[{"name":"The Central Laboratory Jinshan Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"The Molecular Genetic Diagnosis Center, Shanghai Key Laboratory of Birth Defects, Pediatrics Research Institute Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei\u2010Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Sha","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jinshan Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010She","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23539"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1089-3261(05)70139-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.038"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2015.08.037"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.026187"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2012.06.006"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24827"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.07.006"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22683"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053981"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20765"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306555"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.01.006"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164058"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0175-3"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2009.02112.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153114"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-198703000-00006"},{"key":"e_1_2_6_21_1","first-page":"122","article-title":"Structure and function of ABC transporters","volume":"22","author":"Linton KJ","year":"2007","journal-title":"Phys Ther"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.12049"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mpg.0000184429.34001.68"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg775"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215968"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27767"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400182101"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.065"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00367.2007"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhepr.13055","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T18:28:26Z","timestamp":1695493706000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.13055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,12]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/hepr.13055"],"URL":"https:\/\/doi.org\/10.1111\/hepr.13055","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"type":"print","value":"1386-6346"},{"type":"electronic","value":"1872-034X"}],"subject":[],"published":{"date-parts":[[2018,2,12]]}}}