HNF1B deficiency causes ciliary defects in human cholangiocytes.
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 Hnf1β 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.
Hepatology Department, University Hospitals Leuven, Belgium.
Philip
P
Roelandt
Aline
A
Antoniou
Louis
L
Libbrecht
Werner
W
Van Steenbergen
Wim
W
Laleman
Chris
C
Verslype
Schalk
S
Van der Merwe
Frederik
F
Nevens
Rita
R
De Vos
Evelyne
E
Fischer
Marco
M
Pontoglio
Frédéric
F
Lemaigre
David
D
Cassiman
D000328:Adult; D001652:Bile Ducts / Q000166:cytology*; D002923:Cilia; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D051539:Hepatocyte Nuclear Factor 1-beta / Q000172:deficiency*; D006801:Humans; D008297:Male; D008875:Middle Aged
D051539:Hepatocyte Nuclear Factor 1-beta