Diabet. Med. 27, 1195–1200 (2010)

Aims  Permanent neonatal diabetes is a rare condition affecting 1 in 300 000–400 000 live births; only in 60% of cases it is possible to identify the genetic defect. The condition of pancreatic agenesis is rarer still. Only two genes are known to determine this phenotype: PDX‐1 and PTF1A. Congenital heart defects are among the most common developmental anomalies, affecting 1% of newborns, and the GATA4 gene is less frequently involved in these disorders. An Italian child with pancreatic agenesis and an atrial septal defect was genetically investigated to elucidate whether the association of the two pathologies was casual, or represented a new pancreatic/cardiac syndrome.

Methods  A panel of pancreas development genes, including GCK, Kir6.2, PTF1A, PDX‐1, HNF‐1A, NgN3, SOX17, SOX7, SOX9, INS, HNF1‐B and SUR1 plus the GATA4 gene, were screened for characterization of pancreatic agenesis and cardiac defect.

Results  Screening for genes causing permanent neonatal diabetes was negative. A novel mutation in GATA4 (c1512C>T) was detected and functional characterization confirmed a reduced activity of the protein. In the family members, the GATA4 mutation co‐segregates with a cardiac phenotype, but not with pancreatic agenesis.

Conclusions  We describe the first report of pancretic agenesis with an associated cardiac defect and a mutation in the GATA4 gene. We could not establish that the GATA4 mutation was causative for pancreatic agenesis and further genetic investigation to detect the genetic cause of the pancreas agenesis was unsuccessful. We conclude that, the two pathologies are attributable to two independent events.