An in-frame deletion in Kir6.2 (KCNJ11) causing neonatal diabetes reveals a site of interaction between Kir6.2 and SUR1.

ABSTRACT: Activating mutations in genes encoding the Kir6.2 (KCNJ11) and SUR1 (ABCC8) subunits of the pancreatic ATP-sensitive K(+) channel are a common cause of permanent neonatal diabetes (PNDM). All Kir6.2 mutations identified to date are missense mutations. We describe here a novel in-frame deletion (residues 28-32) in Kir6.2 in a heterozygous patient with PNDM without neurological problems that are detectable by standard evaluation. The aim of the study was to identify the mutation responsible for neonatal diabetes in this patient and characterize its functional effects. Wild-type and mutant Kir6.2/SUR1 channels were examined by heterologous expression in Xenopus oocytes. The Kir6.2-28Delta32 mutation produced a significant decrease in ATP inhibition and an increase in whole-cell K(ATP) current

SUBMITTER: Craig TJ 

PROVIDER: S-EPMC7611921 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature