Dual hereditary jaundice: simultaneous occurrence of mutations causing Gilbert's and Dubin-Johnson syndrome
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu kazuistiky, časopisecké články, práce podpořená grantem
PubMed
16012956
DOI
10.1053/j.gastro.2004.10.009
PII: S0016508504019262
Knihovny.cz E-zdroje
- MeSH
- familiární hyperbilirubinemie genetika patologie MeSH
- Gilbertova nemoc komplikace genetika patologie MeSH
- glukuronosyltransferasa genetika MeSH
- lidé MeSH
- membránové transportní proteiny genetika MeSH
- předškolní dítě MeSH
- protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům genetika MeSH
- žloutenka chronická idiopatická komplikace genetika patologie MeSH
- žloutenka genetika patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABCC2 protein, human MeSH Prohlížeč
- glukuronosyltransferasa MeSH
- membránové transportní proteiny MeSH
- protein spojený s mnohočetnou rezistencí k lékům 2 MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům MeSH
- UGT1A1 enzyme MeSH Prohlížeč
BACKGROUND & AIMS: Dubin-Johnson syndrome is recessively inherited, conjugated hyperbilirubinemia induced by mutations in the ABCC2/MRP2 gene encoding the canalicular transporter for conjugated bilirubin. Gilbert's syndrome is recessively inherited, unconjugated hyperbilirubinemia caused by decreased conjugation rate of bilirubin associated mostly with homozygous A(TA) 7 TAA variant of the TATAA-box in the UGT1A1 gene promoter. Our aim was to establish the molecular diagnosis in a 3-year-old male with atypical, intermittent, predominantly unconjugated, hyperbilirubinemia. METHODS: 99m Tc-HIDA cholescintigraphy was used for imaging the biliary tree. Expression of ABCC2/MRP2 protein in hepatocytes was investigated immunohistochemically. UGT1A1 and ABCC2/MRP2 genes were sequenced from genomic DNA, and the mutations were verified by fragment analysis, sequencing the cloned exons, and restriction fragment length polymorphism. RESULTS: Cholescintigraphy revealed delayed visualization of the gallbladder. A brown granular lipopigment differing from melanin-like pigment reported in Dubin-Johnson syndrome was present in hepatocytes, but, otherwise, liver histology was normal. ABCC2/MRP2 protein was not detected on the canalicular membrane of hepatocytes, and 2 novel mutations were found in the ABCC2/MRP2 gene: a heterozygous in-frame insertion-deletion mutation 1256insCT/delAAACAGTGAACCTGATG in exon 10 inherited from the father and a heterozygous deletion 4292delCA in exon 30 inherited from the mother. In addition, the patient was homozygous for -3279T>G and A(TA) 7 TAA mutations in the UGT1A1 gene promoter. CONCLUSIONS: Our patient represents a case of digenic mixed hyperbilirubinemia-a distinct type of constitutive jaundice resulting from coinherited defects in ABCC2/MRP2 and UGT1A1 genes.
Citace poskytuje Crossref.org
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