Supplementary Material for: Two Novel GATA6 Mutations Cause Childhood-Onset Diabetes Mellitus, Pancreas Malformation and Congenital Heart Disease

<b><i>Background:</i></b><i>GATA6</i> 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 <i>GATA6</i> mutations in an independent cohort of 8 children with pancreas aplasia or hypoplasia and diabetes. <b><i>Methods:</i></b> We sequenced <i>GATA6</i> 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. <b><i>Results:</i></b> We found two novel heterozygous <i>GATA6</i> 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. <i>GATA6</i> 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. <b><i>Conclusion:</i></b> Our 2 cases with novel <i>GATA6</i> mutations add more phenotype characteristics of <i>GATA6</i> 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.