title: Characterization of ABCC8 and KCNJ11 gene mutations and phenotypes in Korean patients with congenital hyperinsulinism.
abstract: OBJECTIVE
  Congenital hyperinsulinism (CHI) is characterized by persistent hypoglycemia due to the inappropriate insulin secretion. Inactivating mutations in the ABCC8 and KCNJ11 genes, which encode the sulfonylurea receptor 1 and Kir6.2 subunits of the ATP-sensitive K(+) (K(ATP)) channel in pancreatic β-cell, are the most common cause of CHI. We studied the genetic etiology and phenotypes of CHI in Korean patients.
  
  
  METHODS
  ABCC8 and KCNJ11 mutational analysis was performed in 17 patients with CHI. Medical records were retrospectively reviewed to identify phenotypes.
  
  
  RESULTS
  Mutations (12 ABCC8 and three KCNJ11) were identified in 82% (14/17) of patients. Of these, nine ABCC8 mutations (E100X, W430X, c.1630+1G>C, D813N, Q923X, E1087_A1094delinsDKSDT, Q1134H, H1135W, and E1209Rfs) and one KCNJ11 mutation (W91X) were novel. Of the 14 patients, four had confirming recessively inherited CHI. The remaining ten patients had single heterozygous mutations. The majority (12/17) of patients were medically responsive. Of the five diazoxide-responsive patients, four had an ABCC8 mutation. The five patients unresponsive to medical management and one diazoxide-responsive patient underwent pancreatectomy and had diffuse histology. Of the operated six patients, two had recessively inherited mutations; three patients had a single heterozygous mutation (one maternally and two paternally inherited); and one patient had no identifiable K(ATP) channel mutation.
  
  
  CONCLUSIONS
  This is the first study to report genotype and phenotype correlations among Korean patients with CHI. Mutations in ABCC8 and KCNJ11 are the most common causes of CHI in Korean patients. Similar to other studies, there is marked genetic heterogeneity and no clear genotype-phenotype correlation.
authors.affiliation: Department of Pediatrics, College of Medicine, CHA Gangnam Medical Center, CHA University, 650-9 Yeoksam 1-dong, Gangnam-gu, Seoul 135-914, Republic of Korea.
authors.forename: So Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Choong Ho
authors.initials: CH
authors.lastname: Shin
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Yang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017668:Age of Onset; D044466:Asian People; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003981:Diazoxide / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D006946:Hyperinsulinism / Q000151:congenital* / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics / Q000502:physiology; D015282:Octreotide / Q000627:therapeutic use; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D056910:Republic of Korea; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D004247:DNA; D003981:Diazoxide; D004232:Diuretics; D015282:Octreotide; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel