{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:07:43Z","timestamp":1787602063579,"version":"build-2736575974"},"reference-count":16,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T00:00:00Z","timestamp":1596844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Wilson disease is an autosomal recessive metabolic disorder resulting from accumulation of excess copper especially in the liver and brain. This disease is mainly characterized by hepatic disorders and less frequently by neuro\u2010psychiatric disturbances. This recessive disease is due to mutation in\n                      <jats:italic>ATP7B<\/jats:italic>\n                      , which codes for an ATPase involved in copper\u2010transport across the plasma membrane. Molecular diagnosis of WD is positive in approximately 98% of cases. Also, in few cases, WD patients present a single deleterious mutation (heterozygous) or no mutation after sanger and NGS standard sequencing analysis of\n                      <jats:italic>ATP7B<\/jats:italic>\n                      . Therefore, in these problematic WD cases, we hypothesized that deleterious mutations reside in intronic regions of\n                      <jats:italic>ATP7B<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Complete\n                      <jats:italic>ATP7B<\/jats:italic>\n                      gene was sequenced by Next Generation Sequencing including its promoter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five unrelated families with Wilson disease shared the same novel, deep intronic NG_008806.1 (ATP7B_v001):c.2866\u20101521G&gt;A variant in\n                      <jats:italic>ATP7B<\/jats:italic>\n                      . Analysis of RNA transcripts from primary fibroblasts of one patient confirmed the deleterious impact of the intronic variant on splicing and its likely pathologic effect in this compound heterozygote.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This discovery of a novel intronic mutation in\n                      <jats:italic>ATP7B<\/jats:italic>\n                      has improved the molecular diagnosis of WD in the French patient cohort to greater than 98%. Thus, we recommend complete sequencing of\n                      <jats:italic>ATP7B<\/jats:italic>\n                      gene, including introns, as a molecular diagnostic approach in cases of clinically confirmed WD which lack pathogenic exon or promoter variants in one or both alleles.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1428","type":"journal-article","created":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T04:59:09Z","timestamp":1596862749000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A novel deep intronic variant in\n                    <i>ATP7B<\/i>\n                    in five unrelated families affected by Wilson disease"],"prefix":"10.1002","volume":"8","author":[{"given":"France","family":"Woimant","sequence":"first","affiliation":[{"name":"National reference Centre for Wilson\u2019s Disease (CRMR Wilson) Department of Neurology Rothschild Hospital Paris France"},{"name":"Department of Neurology Lariboisiere University Hospital APHP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelia","family":"Poujois","sequence":"additional","affiliation":[{"name":"National reference Centre for Wilson\u2019s Disease (CRMR Wilson) Department of Neurology Rothschild Hospital Paris France"},{"name":"Department of Neurology Lariboisiere University Hospital APHP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Bloch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Lariboisiere University Hospital APHP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabaras","family":"Jordi","sequence":"additional","affiliation":[{"name":"National reference Centre for Wilson\u2019s Disease (CRMR Wilson) Department of Neurology Rothschild Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Laplanche","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Lariboisiere University Hospital APHP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Lariboisiere University Hospital APHP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-863X","authenticated-orcid":false,"given":"Corinne","family":"Collet","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Lariboisiere University Hospital APHP Paris France"},{"name":"INSERM U1132 University Paris\u2010Diderot and Department of Rheumatology Lariboisiere University Hospital Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(14)70190\u20105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2012.04.024"},{"key":"e_1_2_8_4_1","first-page":"19","volume-title":"Handbook of clinical neurology","author":"Chang I.","year":"2017"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100221\u20104"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt035"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010018\u20100660\u20103"},{"key":"e_1_2_8_8_1","article-title":"DNA: Genetic studies in order of Wilson\u2019s disease diagnosis","author":"Collet C.","year":"2018","journal-title":"EMC Biologie M\u00e9dicale"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20101004(199910)14:4<304:AID\u2010HUMU5>3.0.CO;2\u2010W"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.02.07"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2017.49"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000350"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.13575"},{"key":"e_1_2_8_14_1","first-page":"77","volume-title":"Handbook of clinical neurology","author":"Poujois A.","year":"2017"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2017.05.011"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50252"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13754"}],"container-title":["Molecular Genetics &amp; 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