Analysis of pathogenic gene mutation in 13 cases with congenital hyperinsulinism

Objective To explore the gene mutations of the 13 children diagnosed as congenital hyperinsulinism(CHI). Methods A total of 13 children with CHI (8 boys and 5 girls) hospitalized in Beijing Children's Hospital from September 2006 to November 2015 and their parents were chosen as the study subjects. Genetic sequencing analysis of CHI related genes were done with the second generation sequencing technology. The abrupt change points of the patients were validated with the first generation sequencing technology and the same points in the patients' parents were sequenced as well. Results A W777X heterozygous mutation of ABCC8 gene was detected in case 1, an L1439P heterozygous mutation of ABCC8 gene was detected in case 7 and his father, a R16P heterozygous mutation of ABCC8 gene was detected in case 13 and his father, a N463I heterozygous mutation of GLUD1 gene was detected in case 4, an H507Y heterozygous mutation of GLUD1 gene was detected in case 11, and an E496K heterozygous mutation of SLC16A1 gene was detected in case 9. No mutation was found in the other 7 patients and their parents.The patients showed different responses to diazoxide. Conclusions ABCC8, GLUD1 and SLC16A1 gene mutations can cause CHI. Different gene mutations have different treatment responses to diazoxide. Some patients with glutamate dehydrogenase hyperinsulinism tend to be self-cured. Key words: Congenital hyperinsulinism; Gene mutation; Diazoxide