ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia.

Abstract

PURPOSE:

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.

CONCLUSION:

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: Benjamin Glaser, Ilana Blech, Yocheved Krakinovsky, Josef Ekstein, David Gillis, Kineret Mazor-Aronovitch, Heddy Landau, Dvorah Abeliovich
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 13 Issue 10 Pg. 891-4 (Oct 2011) ISSN: 1530-0366 [Electronic] United States
• PMID: 21716120 (Publication Type: Journal Article)

Chemical References

• ATP-Binding Cassette Transporters
• Potassium Channels, Inwardly Rectifying
• Receptors, Drug
• Sulfonylurea Receptors

Topics

• ATP-Binding Cassette Transporters (genetics)
• Congenital Hyperinsulinism (genetics)
• Female
• Founder Effect
• Gene Frequency
• Genetic Counseling
• Genetic Predisposition to Disease
• Genetic Testing
• Genotype
• Heterozygote
• Humans
• Jews
• Point Mutation
• Potassium Channels, Inwardly Rectifying (genetics)
• Pregnancy
• Receptors, Drug (genetics)
• Risk Factors
• Sequence Deletion
• Sulfonylurea Receptors