What is the genetic association between Gaucher disease and the Ashkenazi Jewish population?
The high frequency of Gaucher disease in the Ashkenazi Jewish population is due to the occurrence of a mutation at nucleotide 1226 of GBA1, the gene that encodes glucocerebrosidase (see genetic inheritance of Gaucher disease). This mutation was identified in >75% of alleles from 57 unrelated Ashkenazi Jewish patients with Gaucher disease, and in 8% of alleles from 50 healthy Jewish volunteers.1,5
An analysis of 593 DNA samples from healthy Ashkenazi Jewish participants revealed that the GBA1 N370S (c.1226A>G; p.Asp409Ser) mutation in the heterozygous state was identified in 37 healthy Ashkenazi Jewish volunteers and in two individuals for the homozygous state. This finding indicates that the gene frequency of the N370S (c.1226A>G; p.Asp409Ser) mutation of GBA1 was 0.035 in healthy Ashkenazi Jews. Genetic analysis showed that the N370S (c.1226A>G; p.Asp409Ser) mutation represented 73% of 124 alleles from Ashkenazi Jewish patients with Gaucher disease, indicating a gene frequency of 0.047, which is equivalent to a carrier frequency of 8.9%.1
Frequency and origin of two genetic mutations associated with Gaucher disease in the Ashkenazi Jewish population: a retrospective analysis
A retrospective analysis aimed to verify the frequency and trace the origin of Gaucher disease mutations in patients of Ashkenazi Jewish ethnicity (confirmed by the birthplace of their grandparents e.g. Austria, the Baltic countries, Belarus, Czech Republic, Germany, Hungary, Moldova, Poland, Romania and the European part of Russia). Gaucher disease carrier status in participants was screened between 2006 and 2011, and mutations were identified using restriction analysis of 16,910 Ashkenazi Jewish alleles. A GBA1 mutation was identified in 509 participants, indicating a carrier rate of 1 in 16.6. N370S (c.1226A>G; p.Asp409Ser) and R496H (c.1604G>A; p.Arg535His) mutations were the most frequent in this population; the carrier frequency of these mutations was 1:19.4 and 1:207, respectively. The ratio of NS70S (c.1226A>G; p.Asp409Ser) and R496H (c.1604G>A; p.Arg535His) carriers in Romania to Poland was 0.547 and 1.11, respectively, compared with 0.52 for normal alleles.6*