(HEPATOLOGY 2012;56:1178–1181) HNF1B (hepatocyte nuclear factor 1 homeobox B) deficiency is the underlying cause of the renal cyst and diabetes syndrome (OMIM #137920), characterized by defects in pancreatic islets leading to maturity onset diabetes of the young (MODY5), and deficiencies in the exocrine pancreas, urogenital tract, Alvelestat manufacturer and liver.1 During

bile duct morphogenesis, HNF1B belongs to a dynamic transcriptional network regulating bile duct formation. Homozygous liver-specific deletion of Hnf1β in mice leads to ductopenia and bile duct dysplasia.2 In humans, heterozygous mutation of HNF1B can result in ductal plate malformations and cholestasis.3 Normal cholangiocytes contain a 7-μm single nonmotile primary cilium, projecting into the lumen and essential for sensory NVP-AUY922 functions. As in all primary cilia, the axoneme contains 9+0 microtubules (compared to 9+1 microtubules in motile cilia).4 Abnormalities in primary cilia lead to a wide variety of diseases affecting different organs, generally classified as ciliopathies.5 We recently showed that mice with homozygous liver-specific Hnf1β knockout mice have absent immunostaining of acetylated tubulin in developing bile ducts, suggesting aberrant ciliogenesis.6 However, the presence of cilia had not yet been investigated in patients

or heterozygous knockout mice at the ultrastructural level. Case 1: A 34-year-old woman was referred because of progressively increasing, mainly cholestatic, liver tests for more than 5 years. She was known to have had diabetes since age 14. Liver biopsy revealed only nonspecific changes and some steatosis. Ultrasound showed atrophy of the pancreas, renal cysts, and a bicornuate uterus, whereas fibroscan confirmed the absence of fibrosis. Case 2: A 53-year-old man with mild mental retardation was followed for 9 years because of “alcohol-induced” chronic pancreatitis. After 7 years of follow-up he was diagnosed with diabetes mellitus, interpreted as the result of chronic pancreatitis. However, laboratory analysis also revealed mild renal insufficiency, elevated liver tests, Ixazomib chemical structure and hypomagnesemia, whereas

ultrasound revealed normal liver, atrophic pancreas, and renal cysts. Fibroscan suggested mild fibrosis. Despite relatively good diabetic control and alcohol stop for several years, there were increasing, mainly cholestatic, liver tests. A liver biopsy revealed only minor sinusoidal dilatation. Case 3: A 30-year-old woman was followed with increasing cholestasis. She was known to have poorly controlled diabetes and renal insufficiency. Despite treatment with ursodeoxycholic acid, cholestatic liver tests were increasing. Ultrasound showed renal cysts and pancreatic atrophy. Liver biopsy showed thickened basal membranes around the bile ducts and minor sinusoidal dilatation. At first sight, these three cases are classical poorly controlled diabetes patients with secondary renal insufficiency (see Table 1 for details).