{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:09:20Z","timestamp":1792001360319,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"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":["81570468"],"award-info":[{"award-number":["81570468"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873543"],"award-info":[{"award-number":["81873543"]}],"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":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>In about 20% of children with cholestasis and normal or low serum gamma\u2010glutamyltransferase (GGT) activity, no aetiology is identified. We sought new genes implicated in paediatric hepatobiliary disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted whole\u2010exome sequencing in 69 children evaluated at our centre from 2011 to 2018 who had low\u2010GGT cholestasis and in whom homozygous\/compound heterozygous predictedly pathogenic variants (PPVs) in\n                      <jats:italic>ATP8B1<\/jats:italic>\n                      ,\n                      <jats:italic>ABCB11<\/jats:italic>\n                      ,\n                      <jats:italic>NR1H4<\/jats:italic>\n                      ,\n                      <jats:italic>MYO5B<\/jats:italic>\n                      or\n                      <jats:italic>TJP2<\/jats:italic>\n                      were not found. Clinical records and findings on light microscopy and transmission electron microscopy of liver biopsy materials were reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In seven patients from seven unrelated families, biallelic PPVs (10 in total) were found in\n                      <jats:italic>USP53<\/jats:italic>\n                      , recently associated with intrahepatic cholestasis. Seven variants were classified as pathogenic: one canonical splicing, c.569\u00a0+\u00a02T\u00a0&gt;\u00a0C, and six nonsense or frameshifting: c.169C\u00a0&gt;\u00a0T (p.Arg57Ter), c.581delA (p.Arg195GlufsTer38), c.831_832insAG (p.Val279GlufsTer16), c.1012C\u00a0&gt;\u00a0T (p.Arg338Ter), c.1426C\u00a0&gt;\u00a0T (p.Arg476Ter) and c.1558C\u00a0&gt;\u00a0T (p.Arg520Ter). Three were likely pathogenic: c.297G\u00a0&gt;\u00a0T (p.Arg99Ser), c.395A\u00a0&gt;\u00a0G (p.His132Arg) and c.878G\u00a0&gt;\u00a0T (p.Gly293Val). In all patients, jaundice began at age\u00a0&lt;7\u00a0months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient now aged 5\u00a0years) except one, who was lost to follow\u2010up. Light microscopy identified intralobular cholestasis, giant\u2010cell change of hepatocytes and perisinusoidal\u2010perihepatocytic and portal\u2010tract fibrosis. Ultrastructural study revealed elongated hepatocyte\u2010hepatocyte tight junctions. One patient was deaf.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      USP53 interacts with the tight junction constituent TJP2.\n                      <jats:italic>TJP2<\/jats:italic>\n                      mutation can cause low\u2010GGT intrahepatic cholestasis, with elongated hepatocyte\u2010hepatocyte tight junctions, as well as deafness. Our findings extend a preliminary report of\n                      <jats:italic>USP53<\/jats:italic>\n                      disease and indicate that\n                      <jats:italic>USP53<\/jats:italic>\n                      mutation may generate a partial phenocopy of\n                      <jats:italic>TJP2<\/jats:italic>\n                      disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.14422","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T02:12:34Z","timestamp":1583201554000},"page":"1142-1150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Low\u2010GGT intrahepatic cholestasis associated with biallelic\n                    <i>USP53<\/i>\n                    variants: Clinical, histological and ultrastructural characterization"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-8304","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"The Department of Paediatrics Jinshan Hospital Fudan University Shanghai China"},{"name":"The Center for Paediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"},{"name":"Department of Paediatrics Shanghai Medical College of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yang","sequence":"additional","affiliation":[{"name":"The Department of Paediatrics Jinshan Hospital Fudan University Shanghai China"},{"name":"The Center for Paediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"},{"name":"Department of Paediatrics Shanghai Medical College of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1149-0979","authenticated-orcid":false,"given":"Jing\u2010Yu","family":"Gong","sequence":"additional","affiliation":[{"name":"The Department of Paediatrics Jinshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-4360","authenticated-orcid":false,"given":"Li\u2010Ting","family":"Li","sequence":"additional","affiliation":[{"name":"The Center for Paediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"},{"name":"Department of Paediatrics Shanghai Medical College of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3150-3212","authenticated-orcid":false,"given":"Jia\u2010Qi","family":"Li","sequence":"additional","affiliation":[{"name":"The Department of Paediatrics Jinshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-7180","authenticated-orcid":false,"given":"Mei\u2010Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Department of Paediatrics Jinshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-4501","authenticated-orcid":false,"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"The Center for Paediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"},{"name":"Department of Paediatrics Shanghai Medical College of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Bao","family":"Xie","sequence":"additional","affiliation":[{"name":"The Center for Paediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"},{"name":"Department of Paediatrics Shanghai Medical College of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Ren","family":"Hong","sequence":"additional","affiliation":[{"name":"Electron Microscopy Core Laboratory Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Yu","sequence":"additional","affiliation":[{"name":"Electron Microscopy Core Laboratory Shanghai Medical College Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-539X","authenticated-orcid":false,"given":"A. S.","family":"Knisely","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie Medizinische Universit\u00e4t Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-586X","authenticated-orcid":false,"given":"Jian\u2010She","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center for Paediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"},{"name":"Department of Paediatrics Shanghai Medical College of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2017.01.006"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0288-x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29020"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.01.006"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164058"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_12_8_1","first-page":"Unit7.20","article-title":"Predicting functional effect of human missense mutations using PolyPhen\u20102","volume":"7","author":"Adzhubei I","year":"2013","journal-title":"Curr Protoc Hum Genet"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1965-15.2015"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26974"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2333"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2016.250"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.12.050"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.05.011"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.171440"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13638"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1147"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2918"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.07.022"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27872"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2204-1"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.14422","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14422","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14422","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T15:37:11Z","timestamp":1694014631000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,7]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/liv.14422"],"URL":"https:\/\/doi.org\/10.1111\/liv.14422","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,7]]},"assertion":[{"value":"2019-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}