GATA4 mutations are a cause of neonatal and childhood-onset diabetes.

2.50
Hdl Handle:
http://hdl.handle.net/11287/618270
Title:
GATA4 mutations are a cause of neonatal and childhood-onset diabetes.
Authors:
Shaw-Smith, Charles; De Franco, Elisa; Lango Allen, H.; Batlle, M.; Flanagan, Sarah; Borowiec, M.; Taplin, C. E.; van Alfen-van der Velden, J.; Cruz-Rojo, J.; Perez de Nanclares, G.; Miedzybrodzka, Z.; Deja, G.; Wlodarska, I.; Mlynarski, W.; Ferrer, J.; Hattersley, Andrew T.; Ellard, Sian ( 0000-0002-7620-5526 )
Abstract:
The GATA family zinc finger transcription factors GATA4 and GATA6 are known to play important roles in the development of the pancreas. In mice, both Gata4 and Gata6 are required for pancreatic development. In humans, GATA6 haploinsufficiency can cause pancreatic agenesis and heart defects. Congenital heart defects also are common in patients with GATA4 mutations and deletions, but the role of GATA4 in the developing human pancreas is unproven. We report five patients with deletions (n = 4) or mutations of the GATA4 gene who have diabetes and a variable exocrine phenotype. In four cases, diabetes presented in the neonatal period (age at diagnosis 1-7 days). A de novo GATA4 missense mutation (p.N273K) was identified in a patient with complete absence of the pancreas confirmed at postmortem. This mutation affects a highly conserved residue located in the second zinc finger domain of the GATA4 protein. In vitro studies showed reduced DNA binding and transactivational activity of the mutant protein. We show that GATA4 mutations/deletions are a cause of neonatal or childhood-onset diabetes with or without exocrine insufficiency. These results confirm a role for GATA4 in normal development of the human pancreas.
Citation:
GATA4 mutations are a cause of neonatal and childhood-onset diabetes. 2014, 63 (8):2888-94 Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
Aug-2014
URI:
http://hdl.handle.net/11287/618270
DOI:
10.2337/db14-0061
PubMed ID:
24696446
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=24696446
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
en
ISSN:
1939-327X
Appears in Collections:
2014 RD&E publications; Diabetes/Endocrine Services; Clinical Genetics (Peninsula Genetics); Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorShaw-Smith, Charlesen
dc.contributor.authorDe Franco, Elisaen
dc.contributor.authorLango Allen, H.en
dc.contributor.authorBatlle, M.en
dc.contributor.authorFlanagan, Sarahen
dc.contributor.authorBorowiec, M.en
dc.contributor.authorTaplin, C. E.en
dc.contributor.authorvan Alfen-van der Velden, J.en
dc.contributor.authorCruz-Rojo, J.en
dc.contributor.authorPerez de Nanclares, G.en
dc.contributor.authorMiedzybrodzka, Z.en
dc.contributor.authorDeja, G.en
dc.contributor.authorWlodarska, I.en
dc.contributor.authorMlynarski, W.en
dc.contributor.authorFerrer, J.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorEllard, Sianen
dc.date.accessioned2016-08-11T15:55:11Z-
dc.date.available2016-08-11T15:55:11Z-
dc.date.issued2014-08-
dc.identifier.citationGATA4 mutations are a cause of neonatal and childhood-onset diabetes. 2014, 63 (8):2888-94 Diabetesen
dc.identifier.issn1939-327X-
dc.identifier.pmid24696446-
dc.identifier.doi10.2337/db14-0061-
dc.identifier.urihttp://hdl.handle.net/11287/618270-
dc.description.abstractThe GATA family zinc finger transcription factors GATA4 and GATA6 are known to play important roles in the development of the pancreas. In mice, both Gata4 and Gata6 are required for pancreatic development. In humans, GATA6 haploinsufficiency can cause pancreatic agenesis and heart defects. Congenital heart defects also are common in patients with GATA4 mutations and deletions, but the role of GATA4 in the developing human pancreas is unproven. We report five patients with deletions (n = 4) or mutations of the GATA4 gene who have diabetes and a variable exocrine phenotype. In four cases, diabetes presented in the neonatal period (age at diagnosis 1-7 days). A de novo GATA4 missense mutation (p.N273K) was identified in a patient with complete absence of the pancreas confirmed at postmortem. This mutation affects a highly conserved residue located in the second zinc finger domain of the GATA4 protein. In vitro studies showed reduced DNA binding and transactivational activity of the mutant protein. We show that GATA4 mutations/deletions are a cause of neonatal or childhood-onset diabetes with or without exocrine insufficiency. These results confirm a role for GATA4 in normal development of the human pancreas.en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=24696446en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleGATA4 mutations are a cause of neonatal and childhood-onset diabetes.en
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalDiabetesen
dc.type.versionPublisheden

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