Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population.
Glycogen storage disease type Ia (GSDIa) is a severe autosomal recessive disorder caused by deficiency of the enzyme D-glucose-6-phosphatase (G6Pase). While numerous mutations have been found in cosmopolitan European populations, Ashkenazi Jewish (AJ) patients appear to primarily carry the R83C mutation, but possibly also the Q347X mutation found generally in Caucasians. To determine the frequency for both these mutations in the AJ population, we tested 20,719 AJ subjects for the R83C mutation and 4,290 subjects for the Q347X mutation. We also evaluated the mutation status of 30 AJ GSDIa affected subjects. From the carrier screening, we found 290 subjects with R83C, for a carrier frequency for this mutation of 1.4%. This carrier frequency translates into a predicted disease prevalence of 1 in 20,000, five times higher than for the general Caucasian population, confirming a founder effect and elevated frequency of GSDIa in the AJ population. We observed no carriers of the Q347X mutation. Among the 30 GSDIa affected AJ subjects, all were homozygous for R83C. These results indicate that R83C is the only prevalent mutation for GSDIa in the Ashkenazi population.
Dor Yeshorim, The Committee for the Prevention of Jewish Genetic Diseases, Brooklyn, New York, USA. jekstein@dor-yeshorim.com
Josef
J
Ekstein
Berish Y
BY
Rubin
Sylvia L
SL
Anderson
David A
DA
Weinstein
Gideon
G
Bach
Dvorah
D
Abeliovich
Michael
M
Webb
Neil
N
Risch
D018703:Founder Effect; D005787:Gene Frequency; D005808:Genes, Recessive; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005953:Glycogen Storage Disease Type I / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational