RARE DISEASE RESEARCH & TRAINING

IPRD funded research by Yue (Julia) Wang, Ph.D.

Congenital hyperinsulinism  is a rare and deadly pediatric disease with an estimated incidence of 1 in 25,000 to 1 in 50,000 births and as high as 1 in 2500 births in consanguineous societies. This disease is often manifested in the neonatal and infant stages. Affected individuals have persistent and dangerously low blood glucose and high insulin levels. The latter further inhibit ketogenesis, lipolysis, and other fuel mobilization processes depleting all energy sources for the brain placing the young patients at extremely high risk of permanent brain damage and long-term neurological complications. Mutations in more than 12 genes, all critical for secretion of insulin from the pancreatic beta cells, are associated with the disease. However, the causative mutations for more than half of the cases are unknown. Furthermore, there is limited understanding on the genotype-phenotype correlations, including the relationship between genetic variants and drug sensitivities. This research project will establish a genomic pipeline to identify structural variants in candidate genes and design targeted genetic panels enabling rapid diagnosis and drug screening.