Background:GATA6 mutations are the most frequent cause of pancreatic agenesis and diabetes in human sporadic cases. In families, dominantly inherited mutations show a variable phenotype also in terms of endocrine and exocrine pancreatic disease. We report two novel GATA6 mutations in an independent cohort of 8 children with pancreas aplasia or hypoplasia and diabetes. Methods: We sequenced GATA6 in 8 children with diabetes and inborn pancreas abnormalities, i.e. hypoplasia or aplasia in which other known candidate genes causing monogenic diabetes and pancreatic defects had been excluded. Results: We found two novel heterozygous GATA6 mutations (c.951_954dup and c.754_904del) in 2 patients with sporadic pancreas hypoplasia, diabetes and severe cardiac defects (common truncus arteriosus and tetralogy of Fallot), but not in the remaining 6 patients. GATA6 mutations in carriers exhibited hypoplastic pancreas with absent head in 1 patient and with increased echogenicity and decreasing exocrine function in the other patient. Additionally, hepatobiliary malformations and brain atrophy were found in 1 patient. Conclusion: Our 2 cases with novel GATA6 mutations add more phenotype characteristics of GATA6 haploinsufficiency. In agreement with an increasing number of published cases, the wide phenotypic spectrum of GATA6 diabetes syndrome should draw the attention of both pediatric endocrinologists and geneticists.

Keywords:
Common truncus arteriosus, GATA6 mutations, Tetralogy of Fallot
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2013
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