13 research outputs found
Clinical evaluation of women with PMB. Is it always necessary an endometrial biopsy to be performed? A review of the literature
Indirect transfers in trade among former Soviet Union Republics: Sources, patterns and policy responses in the Post‐Soviet period
Challenging Incommensurability: What We Can Learn from Ludwik Fleck for the Analysis of Configurational Innovation
Understanding the local policy context of risk management: Competitiveness and adaptation to climate risks in the city of Karlstad, Sweden
HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum.
Journal ArticleAuthor version of article submitted to Nature Reviews Nephrology. The definitive version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrneph.2014.232. First published online 23 Deceember 2014.ReviewHeterozygous 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.Medical Research Council (MRC)National Institute for Health ResearchWellcome Trus