Congenital hyperinsulinism (CHI) is a life-threatening disorder characterized by hypoglycemia due to dysregulated secretion of insulin from pancreatic β-cells. Genetic diagnosis is essential for patient management. NGS technologies give the ability to generate large amounts of sequence data in a relatively short amount of time. We report next generation sequencing (NGS) results in 142 patients (66 boys, 76 girls) with CHI seen at Endocrine Research Centre (Moscow, Russia). The diagnosis of CHI was based on clinical picture (persistent hypoglycemia with onset during neonatal period or early infancy) and confirmed biochemically by the presence of detectable serum insulin during hypoglycemia. NGS was made on Ion Torrent platform and included analysis of the following genes: GCG, GLUD1, WFS1, HNF1A, GCK, INS, HNF1B, ABCC8, HNF4A, RFX6, PTF1A, NEUROD1, AKT2, ZFP57, INSR, EIF2AK3, PPARG, PAX4, PDX1, GLIS3, KCNJ11, SLC16A1, FOXP3, BLK, CEL, KLF11, SCHAD, GCGR. In summary 77 patients (54.2%) were found to carry pathogenic mutations in the CHI related genes. It was estimated that 65 (45.8%) probands had one or more mutations in ABCC8/KCNJ11 genes, 10 patients in GLUD1 (7.0%) and two patients in SCHAD (1.4%). A total of 73 different mutations in 77 patients were found, including 52 ABCC8 mutations (previously reported 23/52), 11 KCNJ11 mutations (previously reported 7/11), eight mutations related to GLUD1 (previously reported 8/8) and 2 heterozygous mutations in SCHAD (not reported before). There were some frequent mutations found in several patients: a combination of monoallelic c.1096G>A:p.G366R in KCNJ11 and c.1038C>G:p.Y344X in ABCC8 was found in 4 children, heterozygous c.G1332T:p.Q444H in ABCC8 occurred in 3 patients and heterozygous c.G4516A:p.E1506K in ABCC8 appeared in 3 patients as well. Therefore, the use of NGS technologies helped to identify genetic cause of CHI in more than half patients.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology