Work

KCNJ11 readthrough variant in a patient with congenital hyperinsulinism

Year: 2025

Type: article

Abstract: 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.

Source: Clinical Pediatric Endocrinology

DOI: 10.1297/cpe.2025-0025