{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:12:46Z","timestamp":1783440766008,"version":"3.54.6"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T00:00:00Z","timestamp":1453939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Education, Science, and Culture of Japan","award":["24659495"],"award-info":[{"award-number":["24659495"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims:<\/jats:title><jats:p>Hereditary unconjugated hyperbilirubinemias, Crigler\u2013Najjar syndrome type I, Crigler\u2013Najjar syndrome type II (CN\u20102), and Gilbert syndrome (GS) all result from mutations of the bilirubin uridine 5'\u2010diphosphate (UDP)\u2010glucuronosyltransferase gene (<jats:italic>UGT1A1<\/jats:italic>). Often, to distinguish between CN\u20102 and GS is difficult because the borderline of the two syndromes is unclear. We analyzed the genotypes and phenotypes of 163 Japanese patients with CN\u20102 or GS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Japanese patients (99 males and 64 females) with unconjugated hyperbilirubinemia were analyzed. Their serum bilirubin concentrations varied from 1.2 to 22.2\u2009mg\/dL (20 to 379\u2009\u03bcM). Genetic analysis of <jats:italic>UGT1A1<\/jats:italic> was performed by PCR\u2010amplified direct sequencing. Association between serum bilirubin concentrations and genotypes group (typical CN\u20102, intermediate group, and typical GS) was studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Most patients had biallelic mutations of <jats:italic>UGT1A1<\/jats:italic>. Moreover, many of them (78.5%) had multiple mutations. The mutation in typical CN\u20102 was a homozygous double missense mutation of p.[G71R:Y486D]. In typical GS group, four prevalent genotypes were detected: homozygous <jats:italic>UGT1A1<\/jats:italic>*<jats:italic>28<\/jats:italic>, <jats:italic>UGT1A1<\/jats:italic>*<jats:italic>6<\/jats:italic>\/<jats:italic>UGT1A1<\/jats:italic>*<jats:italic>28<\/jats:italic>, and homozygous <jats:italic>UGT1A1<\/jats:italic>*<jats:italic>6<\/jats:italic>, and <jats:italic>UGT1A1<\/jats:italic>*<jats:italic>27<\/jats:italic>\/<jats:italic>UGT1A1<\/jats:italic>*<jats:italic>28<\/jats:italic>. In the intermediate group, three genotypes, p.[G71R:Y486D]\/<jats:italic>UGT1A1<\/jats:italic>*<jats:italic>7<\/jats:italic>, p.[G71R:Y486D]\/<jats:italic>UGT1A1<\/jats:italic>*<jats:italic>6<\/jats:italic>, and homozygous <jats:italic>UGT1A1<\/jats:italic>*<jats:italic>7<\/jats:italic>, were detected. Serum bilirubin concentrations of typical CN\u20102, intermediate group, and typical GS are respectively 12.9\u2009\u00b1\u20095.1, 5.2\u2009\u00b1\u20092.2, and 2.8\u2009\u00b1\u20091.1\u2009mg\/dL. Serum bilirubin concentration among the three groups is statistically different (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The serum bilirubin concentration varied continuously from GS to CN\u20102 depending on genotypes. Because of the combination of the mutations and polymorphisms, many patients showed intermediate serum bilirubin concentration between two syndromes. Clinically, it is difficult to distinguish clearly between the two syndromes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.13071","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T17:38:11Z","timestamp":1438882691000},"page":"403-408","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Genotype of <i>UGT1A1<\/i> and phenotype correlation between Crigler\u2013Najjar syndrome type II and Gilbert syndrome"],"prefix":"10.1111","volume":"31","author":[{"given":"Yoshihiro","family":"Maruo","sequence":"first","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayuri","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahide","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Mimura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition Nagoya Bunri University  Inazawa Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shiga University of Medical Science  Otsu Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,1,28]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1715","volume-title":"Principles of Internal Medicine","author":"Berk PD","year":"2001"},{"key":"e_1_2_6_3_1","first-page":"169","article-title":"Congenital familial nonhemolytic jaundice with kernicterus","volume":"10","author":"Crigler JF","year":"1952","journal-title":"Pediatrics"},{"key":"e_1_2_6_4_1","first-page":"241","article-title":"La chol\u00e9mie simple familiale","volume":"21","author":"Gilbert A","year":"1901","journal-title":"Sem. 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