GATA6 inactivating mutations are associated with heart defects and, inconsistently, with pancreatic agenesis and diabetes

Excerpt

To the Editor: Pancreatic agenesis is an extremely rare cause of permanent neonatal diabetes mellitus (NDM) in humans. It can be associated with severe intrauterine growth retardation as well as a plethora of abnormalities or malformations in the heart, biliary tract, gut, thyroid or brain [1‐3]. To date, mutations in three genes have been shown to cause pancreatic agenesis, namely, PDX1 [1], PTF1A [2], and most recently GATA6 [3], all three of which encode transcription factors. The GATA6 study reported heterozygous coding mutations in a dozen individuals with permanent NDM presumed to be due to pancreatic agenesis [3]. The genetic evidence supporting the pathogenicity of these mutations seemed quite strong as the reported mutations had arisen de novo and none of these mutations was present in the 1,000 Genome Project database [3]. The authors concluded that GATA6 may have a key role in human pancreatic development, with strong implications for beta cell regenerative medicine in diabetes [3]. In the present study, we aimed to qualify this conclusion by reporting a case study of a non-consanguineous family. …