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

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

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 inh...

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Bibliographic Details
Published in:Genetics in medicine Vol. 13; no. 10; pp. 891 - 894
Main Authors: Glaser, Benjamin, Blech, Ilana, Krakinovsky, Yocheved, Ekstein, Josef, Gillis, David, Mazor-Aronovitch, Kineret, Landau, Heddy, Abeliovich, Dvorah
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01-10-2011
Elsevier Limited
Subjects:
631/208/457
631/208/737
692/699/317
ATP-Binding Cassette Transporters - genetics
Biomedical and Life Sciences
Biomedicine
Congenital diseases
Congenital Hyperinsulinism - genetics
Female
Founder Effect
Gene Frequency
Genetic Counseling
Genetic Predisposition to Disease
Genetic Testing
Genotype
Heterozygote
Human Genetics
Humans
Hypoglycemia
Jewish people
Jews
Laboratory Medicine
Mutation
Point Mutation
Potassium Channels, Inwardly Rectifying - genetics
Pregnancy
Receptors, Drug - genetics
Risk Factors
Sequence Deletion
Sulfonylurea Receptors
Hyperinsulinemic hypoglycemia
Ashkenazi Jews
ABCC8
SUR1
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Summary: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.
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ISSN:1098-3600
1530-0366
DOI:10.1097/GIM.0b013e31821fea33