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

Charles Shaw-Smith, Elisa De Franco, Hana Lango Allen, Marta Batlle, Sarah E Flanagan, Maciej Borowiec, Craig E Taplin, Janiëlle van Alfen-van der Velden, Jaime Cruz-Rojo, Guiomar Perez de Nanclares, Zosia Miedzybrodzka, Grazyna Deja, Iwona Wlodarska, Wojciech Mlynarski, Jorge Ferrer, Andrew T Hattersley, Sian Ellard

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


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 are also common in patients with GATA4 mutations and deletions but the role of GATA4 in the developing human pancreas is unproven.We report 5 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 post mortem. 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.

Original languageEnglish
Pages (from-to)2888-2894
Number of pages7
Issue number8
Early online date2 Apr 2014
Publication statusPublished - Aug 2014


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