HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum

2.50
Hdl Handle:
http://hdl.handle.net/11287/593927
Title:
HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum
Authors:
Clissold, Rhian L. ( 0000-0002-3090-3492 ) ; Hamilton, Alexander J.; Hattersley, Andrew T.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Bingham, Coralie
Abstract:
Heterozygous mutations in the gene that encodes the transcription factor hepatocyte nuclear factor 1beta (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 approximately 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.
Citation:
Nat Rev Nephrol. 2015 Feb;11(2):102-12.
Publisher:
Nature
Journal:
Nature reviews. Nephrology
Issue Date:
1-Feb-2015
URI:
http://hdl.handle.net/11287/593927
DOI:
10.1038/nrneph.2014.232
PubMed ID:
25536396
Additional Links:
http://dx.doi.org/10.1038/nrneph.2014.232
Type:
Journal Article; Research Support, Non-U.S. Gov't; Review
Language:
eng
ISSN:
1759-507X
Appears in Collections:
2015 RD&E publications; Molecular Genetics; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorClissold, Rhian L.en
dc.contributor.authorHamilton, Alexander J.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorBingham, Coralieen
dc.date.accessioned2016-01-19T12:37:27Zen
dc.date.available2016-01-19T12:37:27Zen
dc.date.issued2015-02-01en
dc.identifier.citationNat Rev Nephrol. 2015 Feb;11(2):102-12.en
dc.identifier.issn1759-507Xen
dc.identifier.pmid25536396en
dc.identifier.doi10.1038/nrneph.2014.232en
dc.identifier.urihttp://hdl.handle.net/11287/593927en
dc.description.abstractHeterozygous mutations in the gene that encodes the transcription factor hepatocyte nuclear factor 1beta (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 approximately 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.en
dc.language.isoengen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/nrneph.2014.232en
dc.titleHNF1B-associated renal and extra-renal disease-an expanding clinical spectrumen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.typeReviewen
dc.identifier.journalNature reviews. Nephrologyen

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