Congenital Hyperinsulinism Research Laboratory

The goal of the Congenital Hyperinsulinism Research Lab is to identify genotype-phenotype correlations in the various genetic forms of congenital hyperinsulinemic hypoglycemia in order to improve diagnosis and management. In particular, the lab, led by Charles Stanley, MD, has sought to understand the relationships between genotype and responsiveness to medical therapy with the KATP-channel agonist, diazoxide, in controlling insulin secretion. The Stanley lab works in tandem with Diva D. De León-Crutchlow, MD, MSCE, director of the Congenital Hyperinsulinism Center, which was originally founded by Dr. Stanley. The lab collaborates with Arupa Ganguly, director of the Genetic Diagnostic Laboratory at the University of Pennsylvania, who established CLIA-certified testing for all known HI genes. When novel variants in known genes are detected, the lab seeks to classify these variants as benign or pathogenic by cascade testing in other family members as well as by phenotyping individuals who carry the novel variant. In vitro functional studies, performed in collaboration with Show-Ling Shyng, PhD, professor at Oregon Health and Science University, are also used as a means to classify mutations.

Because many children with hyperinsulinism do not have an identified mutation in one of the nine genes known to be associated with HI, the laboratory also seeks to identify novel molecular mechanisms in these children and families without a gene mutation. Next-generation sequencing of pancreatic tissue from children who have undergone surgical resection is used to detect low-level mosaic mutation in known HI genes that may be missed using standard sequencing methods. In addition, next-generation sequencing including whole exome or whole genome sequencing is used to detect mutations in novel genes that may be associated with hyperinsulinism in children with negative mutation analysis of known genes. 

Project Highlights

• Mutation Detection
  • Dr. Ganguly has established CLIA-certified testing for all known HI genes.
  • Next-Generation Sequencing is performed on a research basis in the blood or pancreas to detect either low-level mosaic mutation in known genes or mutations in novel genes.  
• Mutation Characterization
  • Genotype-Phenotype correlation
  • Cascade mutation testing in family members
  • Phenotype testing in adult mutation carriers