KCNJ11 readthrough variant in a patient with congenital hyperinsulinism.

KCNJ11 is one of the major causative genes for congenital hyperinsulinism (CHI) characterized by neonatal and infantile hypoglycemia. Although one readthrough KCNJ11 variant has been identified in a patient with CHI, the pathogenicity of the substitution has yet to be confirmed. Here, we identified two heterozygous nucleotide substitutions separated by one nucleotide (c.[1170C>T;1172G>T], alternative description, c.1170_1172delinsTTT) in one allele of KCNJ11 in a neonate with CHI and his father with mild CHI-compatible features. The c.1170C>T and c.1172G>T variants were assumed to be silent p.(Ser390Ser) and readthrough p.(Ter391LeuextTer93) substitutions, respectively. These results suggest that a mutant KCNJ11 protein containing 93 additional amino acids at the C-terminus is likely to exert dominant-negative effects on the wildtype protein and that monoallelic KCNJ11 readthrough variants constitute a rare etiology of CHI.