{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:14:34Z","timestamp":1787015674094,"version":"build-2736575974"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T00:00:00Z","timestamp":1538956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2011\/02\/A\/NZ5\/00339"],"award-info":[{"award-number":["2011\/02\/A\/NZ5\/00339"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2013\/11\/B\/NZ2\/00130"],"award-info":[{"award-number":["2013\/11\/B\/NZ2\/00130"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>\n                      Wilson's disease (WD) is an autosomal recessive disorder associated with disease\u2010causing alterations across the\n                      <jats:italic>ATP7B<\/jats:italic>\n                      gene, with highly variable symptoms and age of onset. We aimed to assess whether the clinical variability of WD relates to modifier genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 248 WD patients were included, of whom 148 were diagnosed after age of 17. Human exome libraries were constructed using AmpliSeq technology and sequenced using the IonProton platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ATP7B<\/jats:italic>\n                      p.His1069Gln mutation was present in 215 patients, with 112 homozygotes and 103 heterozygotes. Three other mutations: p.Gln1351Ter, p.Trp779Ter and c.3402delC were identified in &gt;10 patients. Among patients, 117 had a homozygous mutation, 101 were compound heterozygotes, 27 had one heterozygous mutation, and 3 other patients had no identifiable pathogenic variant of\n                      <jats:italic>ATP7B<\/jats:italic>\n                      . Sixteen mutations were novel, found as part of a compound mutation or as a sole, homozygous mutation. For disease phenotype prediction, age at diagnosis was a deciding factor, while frameshift allelic variants of\n                      <jats:italic>ATP7B<\/jats:italic>\n                      and being male increased the odds of developing a neurological phenotype. Rare allelic variants in\n                      <jats:italic>ESD<\/jats:italic>\n                      and\n                      <jats:italic>INO80<\/jats:italic>\n                      increased and decreased chances for the neurological phenotype, respectively, while rare variants in\n                      <jats:italic>APOE<\/jats:italic>\n                      and\n                      <jats:italic>MBD6<\/jats:italic>\n                      decreased the chances of WD early manifestation. Compound mutations contributed to earlier age of onset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In a Polish population, genetic screening for WD may help genotype for four variants (p.His1069Gln, p.Gln1351Ter, p.Trp779Ter and c.3402delC), with direct sequencing of all\n                      <jats:italic>ATP7B<\/jats:italic>\n                      amplicons as a second diagnostic step. We also identified some allelic variants that may modify a WD phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.13967","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T06:40:02Z","timestamp":1537339202000},"page":"177-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Whole\u2010exome sequencing identifies novel pathogenic variants across the\n                    <i>ATP7B<\/i>\n                    gene and some modifiers of Wilson's disease phenotype"],"prefix":"10.1111","volume":"39","author":[{"given":"Anna","family":"Kluska","sequence":"first","affiliation":[{"name":"Department of Genetics Cancer Center\u2010Institute Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kulecka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Centre of Postgraduate Medical Education Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Litwin","sequence":"additional","affiliation":[{"name":"Department of Neurology Institute of Psychiatry and Neurology Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Dziezyc","sequence":"additional","affiliation":[{"name":"Department of Neurology Institute of Psychiatry and Neurology Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Balabas","sequence":"additional","affiliation":[{"name":"Department of Genetics Cancer Center\u2010Institute Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Piatkowska","sequence":"additional","affiliation":[{"name":"Department of Genetics Cancer Center\u2010Institute Warsaw 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