Update of variants identified in the pancreatic β‐cell K <sub>ATP</sub> channel genes <i>KCNJ11</i> and <i>ABCC8</i> in individuals with congenital hyperinsulinism and diabetes
Elisa De Franco, Cécile Saint‐Martin, Klaus Brusgaard, Amy E. Knight Johnson, Lydia Aguilar‐Bryan, Pamela Bowman, Jean‐Baptiste Arnoux, Annette Rønholt Larsen, May Sanyoura, Siri Atma W. Greeley, Raúl Calzada‐León, Bradley Harman, Jayne Houghton, Elisa Nishimura‐Meguro, Thomas W. Laver, Sian Ellard, Daniela del Gaudio, Henrik Thybo Christesen, Christine Bellanné‐Chantelot, Sarah E. Flanagan
Abstract
The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.