CHI
Exome sequencing in congenital hyperinsulinism
Congenital hyperinsulinism of infancy (CHI) is a rare disorder characterized by severe hypoglycemia due to inappropriate insulin secretion.  The genetic causes of CHI have been found in genes regulating insulin secretion from pancreatic ß-cells; recessive inactivating mutations in the ABCC8 and KCNJ11 genes represent the most common events.  Despite the advances in understanding the molecular pathogenesis of CHI, specific genetic determinants in about 50 % of the CHI patients remain unknown, suggesting additional locus heterogeneity.  In order to search for novel loci contributing to the pathogenesis of CHI, we combined a family-based association study, using the transmission disequilibrium test on 17 CHI patients lacking mutations in ABCC8/KCNJ11, with a whole-exome sequencing analysis performed on 10 probands.  This strategy allowed the identification of the potential causative mutations in genes implicated in the regulation of insulin secretion.