Disruption of HNF1? binding site causes inherited severe unconjugated hyperbilirubinemia
Küçük Resim Yok
Tarih
2015
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Crigler-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.
Açıklama
Anahtar Kelimeler
Crigler-Najjar syndrome, HNF1?, Promoter mutation, Transcriptional regulation, UGT1A1
Kaynak
Journal of Hepatology
WoS Q Değeri
Scopus Q Değeri
N/A
Cilt
63
Sayı
6
