Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

HNF1B-associated Anomalies of the Kidney and the Urinary Tract (CAKUT) [Q63.9]

OMIM numbers: 137920, 189907 (HNF1B)

PD Dr. med. Julia Höfele

Scientific Background

Congenital Anomalies of the Kidney and Urinary Tract, CAKUT, are found in approx. 3-6 per 1,000 newborns and are the main cause for chronic kidney failure during childhood. Mutations were identified in several genes associated with CAKUT. CAKUT comprises a large spectrum of structural and functional malformations, leading to a defect in morphogenesis of the kidneys and/or urinary tract. The phenotypic spectrum of CAKUT ranges from vesicoureteral reflux to renal agenesis.

HNF-1β, a transcription factor, is considered to be an essential factor for embryonic development of the kidneys and the urinary tract, the pancreas and the liver. Mutations and deletions in the encoding HNF1B gene are mainly seen in patients with bilateral renal malformations (renal hypoplasia, multicystic dysplastic kidneys (MCDK), polycystic kidneys and solitary kidneys) as well as in patients with MODY diabetes type 5. Furthermore, there are indications for oligogenic inheritance in patients with autosomal dominant polycystic kidney disease ADPKD), i.e. a mutation can be detected in the PKD1 gene as well as in the HNF1B gene. This pattern of inheritance may be an explanation for the intrafamilial variability of ADPKD.