title: HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum.
abstract: Heterozygous mutations in the gene that encodes the transcription factor hepatocyte nuclear factor 1β (HNF1B) represent the most common known monogenic cause of developmental kidney disease. Renal cysts are the most frequently detected feature of HNF1B-associated kidney disease; however, other structural abnormalities, including single kidneys and renal hypoplasia, and electrolyte abnormalities can also occur. Extra-renal phenotypes might also be observed; consequently, HNF1B-associated disease is considered a multi-system disorder. Other clinical features include early-onset diabetes mellitus, pancreatic hypoplasia, genital tract malformations, abnormal liver function and early-onset gout. Heterozygous mutations in the coding region or splice sites of HNF1B, and complete gene deletion, each account for ∼50% of all cases of HNF1B-associated disease, respectively, and often arise spontaneously. There is no clear genotype-phenotype correlation, consistent with haploinsufficiency as the disease mechanism. Data from animal models suggest that HNF1B has an important function during several stages of nephrogenesis; however, the precise signalling pathways remain to be elucidated. This Review discusses the genetics and molecular pathways that lead to disease development, summarizes the reported renal and extra-renal phenotypes, and identifies areas for future research in HNF1B-associated disease.
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, Devon, UK.
authors.forename: Rhian L
authors.initials: RL
authors.lastname: Clissold
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, Devon, UK.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Hamilton
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, Devon, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.affiliation: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW, Devon, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.affiliation: Renal Unit, Royal Devon and Exeter Hospital, Barrack Road, Exeter EX2 5DW, Devon, UK.
authors.forename: Coralie
authors.initials: C
authors.lastname: Bingham
mesh_terms: D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: D051539:Hepatocyte Nuclear Factor 1-beta