Mutational analysis of ABCC8, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism.

We conducted a cohort study to elucidate the molecular spectrum of congenital hyperinsulinism (CHI) in Chinese pediatric patients. Thirty Chinese children with CHI were chosen as research subjects, 16 of whom were responsive to diazoxide and 13 of whom were not (1 patient was not given the drug for medical reasons). All exons of the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel) genes KCNJ11 and ABCC8, the hepatocyte nuclear factor 4 α (HNF4A) gene, and the Glucokinase (GCK) gene as well as exons 6 and 7 and 10-12 of the glutamate dehydrogenase 1 (GLUD1) gene were amplified from genomic DNA and directly sequenced. Mutations were identified in 14 of 30 patients (47%): 3 in GLUD1 (10%) and 11 in the KATP channel genes (37%). Six patients had paternally derived monoallelic KATP channel mutations predictive of the focal CHI form. We found a novel de novo ABCC8 mutation, p. C1000*, a novel paternally inherited ABCC8 mutation, D1505H, and a dominantly inherited ABCC8 mutation, R1217K. The GLUD1 activating mutation R269H was found in 2 patients: 1 de novo and the other paternally inherited. A de novo S445L mutation was found in 1 patient. No significant HNF4A or GCK mutations were found. CHI has complex genetic onset mechanisms. Paternally inherited monoallelic mutations of ABCC8 and KCNJ11 are likely the main causes of KATP-CHI in Chinese patients. Glutamate dehydrogenase-CHI is the second most common cause of CHI, while HNF4A and GCK are rare types of CHI in Chinese patients.