Disruption of HNF1? binding site causes inherited severe unconjugated hyperbilirubinemia

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dc.contributor.authorVan Dijk R.
dc.contributor.authorMayayo-Peralta I.
dc.contributor.authorAronson S.J.
dc.contributor.authorKattentidt-Mouravieva A.A.
dc.contributor.authorVan Der Mark V.A.
dc.contributor.authorDe Knegt R.
dc.contributor.authorOruc N.
dc.contributor.authorBeuers U.
dc.contributor.authorBosma P.J.
dc.date.accessioned2019-10-27T08:21:04Z
dc.date.available2019-10-27T08:21:04Z
dc.date.issued2015
dc.departmentEge Üniversitesien_US
dc.description.abstractCrigler-Najjar syndrome presents as severe unconjugated hyperbilirubinemia and is characteristically caused by a mutation in the UGT1A1 gene, encoding the enzyme responsible for bilirubin glucuronidation. Here we present a patient with Crigler-Najjar syndrome with a completely normal UGT1A1 coding region. Instead, a homozygous 3 nucleotide insertion in the UGT1A1 promoter was identified that interrupts the HNF1? binding site. This mutation results in almost complete abolishment of UGT1A1 promoter activity and prevents the induction of UGT1A1 expression by the liver nuclear receptors CAR and PXR, explaining the lack of a phenobarbital response in this patient. Although animal studies have revealed the importance of HNF1? for normal liver function, this case provides the first clinical proof that mutations in its binding site indeed result in severe liver pathology stressing the importance of promoter sequence analysis. © 2015 European Association for the Study of the Liver.en_US
dc.identifier.doi10.1016/j.jhep.2015.07.027en_US
dc.identifier.endpage1529en_US
dc.identifier.issn0168-8278
dc.identifier.issue6en_US
dc.identifier.pmid26220753en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage1525en_US
dc.identifier.urihttps://doi.org/10.1016/j.jhep.2015.07.027
dc.identifier.urihttps://hdl.handle.net/11454/25908
dc.identifier.volume63en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Hepatologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCrigler-Najjar syndromeen_US
dc.subjectHNF1?en_US
dc.subjectPromoter mutationen_US
dc.subjectTranscriptional regulationen_US
dc.subjectUGT1A1en_US
dc.titleDisruption of HNF1? binding site causes inherited severe unconjugated hyperbilirubinemiaen_US
dc.typeArticleen_US

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