{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T15:14:31Z","timestamp":1789744471712,"version":"4.0.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":8523,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,5]]},"abstract":"<jats:title>\n                           <jats:bold>ABSTRPlCT<\/jats:bold>\n                        <\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Crigler\u2013Najjar syndrome, type I is a heterogeneous disorder that may result from mutations of various regions of the bilirubin\u2013UDP\u2013glucuronosyltransferase gene complex that encodes two bilirubin\u2013UDP\u2013glucuronosyltransferase isoforms and a phenol\u2013UDP\u2013glucuronosyltransferase isoform in the human liver. The two bilirubin\u2013UDP\u2013glucuronosyltransferase messenger RNAs and the phenol\u2013UDP\u2013glucuronosyltransferase messenger RNA have identical 3\u2032 regions derived from four consecutive exons. The 5\u2032 region of each messenger RNA is unique and is derived from distinct single exons. By screening a human genomic library with probes corresponding to various regions of the messenger RNAs, we have isolated five cosmid clones containing overlapping segments of this large gene complex that spans at least 84 kb of the human genome. To facilitate the amplification of each exon by polymerase chain reaction and their adjacent splice junctions, we have delineated the intron\u2013exon boundaries of the four common region exons and the two single exons that encode the unique regions of the two bilirubin\u2013UDP\u2013glucuronosyltransferase isoforms and have described sequences of the regions flanking each exon. All exons encoding the two bilirubin\u2013UDP\u2013glucuronosyltransferase isoforms and their splice junctions were amplified from the DNA of two control subjects and a Crigler\u2013Najjar syndrome, type I patient. The DNA from the Crigler\u2013Najjar syndrome, type I patient revealed a point mutation in exon 3 (a common region exon) resulting in a stop codon. RNA blot showed that the two bilirubin\u2013UDP\u2013glucuronosyltransferase messenger RNAs in the liver of the Crigler\u2013Najjar syndrome, type I patient were of normal length but were reduced in concentration. As expected, the mutation was found in the common region of both bilirubin\u2013UDP\u2013glucuronosyltransferase messenger RNAs in the liver of the patient. The premature stop codon is predicted to encode truncated and inactive bilirubin\u2013UDP\u2013glucuronosyltransferase forms. Bilirubin\u2013UDP\u2013glucuronosyltransferase proteins were not detectable by immunotransblot in the liver of the Crigler\u2013Najjar syndrome, type I patient. The single mutation in a common region exon explains the simultaneous loss of activity of both bilirubin\u2013UDP\u2013glucuronosyltransferase isoforms and marked reduction of UDP\u2013glucuronosyltransferase activity toward phenol. (Hepatology 1992;15:941-947).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840150531","type":"journal-article","created":{"date-parts":[[2007,3,4]],"date-time":"2007-03-04T00:43:08Z","timestamp":1172968988000},"page":"941-947","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":154,"title":["Sequence of Exons and the Flanking Regions of Human Bilirubin\u2013Udp\u2013Glucuronosyltransferase Gene Complex and Identification of A Genetic Mutation in A Patient With Crigler\u2013Najjar Syndrome, Type I"],"prefix":"10.1097","volume":"15","author":[{"given":"Piter J.","family":"Bosma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namita Roy","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart G.","family":"Goldhoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H.","family":"Hofker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald P.J.","family":"Oude Elferink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.M.","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanta Roy","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840150531-BIB1","volume-title":"Glucuronidation of drugs and other compounds","author":"Dutton","year":"1980","unstructured":"Glucuronidation of drugs and other compounds. 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Detection of gene expression. In: ed. PCR technology: principles and applications of DNA amplification. 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