title: ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia.
abstract: OBJECTIVE
  Congenital hyperinsulinism of infancy (OMIM# 256450) is a devastating disease most commonly caused by dominant or recessive mutations in either ABCC8 or KCNJ11, the genes that encode for the β-cell adenosine triphosphate-regulated potassium channel. A unique combination of a paternally inherited germline mutation and somatic loss-of-heterozygosity causes the focal form of the disease (Focal-congenital hyperinsulinism of infancy [Focal-CHI]), the incidence of which in genetically susceptible individuals is not known.
  
  
  METHODS
  We genotyped 21,122 Ashkenazi Jewish individuals for two previously identified ABCC8 founder mutations and utilized a clinical database of 61 unrelated Ashkenazi patients with congenital hyperinsulinism of infancy to obtain an estimate of the risk of Focal-CHI in a genetically susceptible fetus.
  
  
  RESULTS
  The combined mutation carrier rate in Ashkenazi Jews was 1:52, giving an estimated frequency of homozygosity or compound heterozygosity of 1:10,816 in this population. The risk of Focal-CHI is 1:540 per pregnancy in offspring of carrier fathers.
  
  
  CONCLUSIONS
  We recommend that these mutations be included in the genetic screening program for the Ashkenazi Jewish population. As the risk of Focal-CHI is not expected to be mutation specific, the data reported in this study are useful for counseling all families in which the father was found to carry a recessive ABCC8 or KCNJ11 mutation.
authors.affiliation: Internal Medicine Department, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. beng@cc.huji.ac.il
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaser
authors.forename: Ilana
authors.initials: I
authors.lastname: Blech
authors.forename: Yocheved
authors.initials: Y
authors.lastname: Krakinovsky
authors.forename: Josef
authors.initials: J
authors.lastname: Ekstein
authors.forename: David
authors.initials: D
authors.lastname: Gillis
authors.forename: Kineret
authors.initials: K
authors.lastname: Mazor-Aronovitch
authors.forename: Heddy
authors.initials: H
authors.lastname: Landau
authors.forename: Dvorah
authors.initials: D
authors.lastname: Abeliovich
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D044903:Congenital Hyperinsulinism / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007585:Jews; D017354:Point Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011247:Pregnancy; D011955:Receptors, Drug / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors