HNF1B is a transcription factor regulating expression of a large number of genes essential for the development of the kidney, liver, pancreas and genital tract. A mutation in HNF1B consequently leads to structural and functional abnormalities of these organs. Mutations in HNF1B consist of base substitutions, small insertions/deletions or deletion of the 17q12 chromosome which includes the HNF1B gene. Most mutations cluster in the first four exons of the gene which encode for the dimerization and DNA-binding domain. Currently, over 50 different HNF1B mutations have been reported to be pathogenic. No correlations have been identified between the type or position of the mutation and the phenotype of ADTKD-HNF1B patients. In contrast, the whole gene deletion caused by the 17q12 deletion is associated with autism. Diagnosing patient is typically very difficult due to the large phenotypic variability between patients. This large variability could be explained by several factors including genetic variants in HNF1B interacting proteins (1), mutations or variation in genes that are in the same biological pathways as HNF1B (2) and variations in non-coding regions of the DNA that affect HNF1B genes expression (3).
HNF1B