{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:31:17Z","timestamp":1775842277446,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"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":["81600405"],"award-info":[{"award-number":["81600405"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Wilson disease is an inborn error of metabolism caused by abnormalities of the copper\u2010transporting protein\u2010encoding gene <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic>. Recently, the phenomenon of exon skipping, in which exonic mutations result in abnormal splicing, has been associated with various diseases. The present study investigated the splicing defects of the <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic> exonic variants identified in a cohort of 44 patients with Wilson disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>All patients were analysed for <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic> gene by direct sequencing or multiplex ligation\u2010dependent probe amplification analysis. To identify the potential pathogenicity of the candidate mutations that may induce exon skipping, both in vivo <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> analysis using <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> from peripheral leukocytes and in vitro functional splicing by minigene construction were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patterns of inheritance of the mutations in <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic> identified in 44 patients exhibited homozygotes (7 patients), compound heterozygotes (32 patients) and heterozygotes (5 patients). In all patients, we detected 25 different <jats:italic><jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B<\/jats:italic> mutations, including 17 missenses, 1 frameshift, 3 nonsenses, 2 exonic deletions and 2 splicing alteration. In these mutations, 4 mutations have not been previously described in the literature or entered in human genome mutation database. Furthermore, we identified synonymous mutation c.4014T&gt;A and missense mutation R919G caused exon skipping in the <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>7B <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> transcript.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that aberrant exon skipping associated to putative splicing enhancer disruption and silencer creation is one previously unrecognized mechanism in Wilson disease. What is more, the multiplex ligation\u2010dependent probe amplification assay for the detection of exon deletions may be valuable in individuals with clinical Wilson disease diagnosis where one or no mutation has been identified by sequencing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13754","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T03:24:16Z","timestamp":1523417056000},"page":"1504-1513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Presumed missense and synonymous mutations in <scp>ATP<\/scp>7B gene cause exon skipping in Wilson disease"],"prefix":"10.1111","volume":"38","author":[{"given":"Chunli","family":"Wang","sequence":"first","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University  Nanjing 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