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HNF1B deficiency causes ciliary defects in human cholangiocytes
Author(s) -
Roelandt Philip,
Antoniou Aline,
Libbrecht Louis,
Van Steenbergen Werner,
Laleman Wim,
Verslype Chris,
Van der Merwe Schalk,
Nevens Frederik,
De Vos Rita,
Fischer Evelyne,
Pontoglio Marco,
Lemaigre Frédéric,
Cassiman David
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25876
Subject(s) - hnf1b , cholestasis , bile duct , hepatocyte nuclear factors , cilium , homeobox , hepatocyte , biology , medicine , pathology , transcription factor , endocrinology , genetics , gene , in vitro
Heterozygous deletion or mutation in hepatocyte nuclear factor 1 homeobox B/transcription factor 2 ( HNF1B/TCF2 ) causes renal cyst and diabetes syndrome (OMIM #137920). Mice with homozygous liver‐specific deletion of Hnf1 β revealed that a complete lack of this factor leads to ductopenia and bile duct dysplasia, in addition to mild hepatocyte defects. However, little is known about the hepatic consequences of deficient HNF1B function in humans. Three patients with heterozygous HNF1B deficiency were found to have normal bile duct formation on radiology and routine liver pathology. Electron microscopy revealed a paucity or absence of normal primary cilia. Therefore, heterozygous HNF1B deficiency is associated with ciliary anomalies in cholangiocytes, and this may cause cholestasis. (H EPATOLOGY 2012;56:1178–1181)