<i>KCNJ11</i> readthrough variant in a patient with congenital hyperinsulinism

<i>KCNJ11</i> is one of the major causative genes for congenital hyperinsulinism (CHI) characterized by neonatal and infantile hypoglycemia. Although one readthrough <i>KCNJ11</i> 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 <i>KCNJ11</i> 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 <i>KCNJ11</i> readthrough variants constitute a rare etiology of CHI.