title: An update of Gaucher mutations distribution in the Ashkenazi Jewish population: prevalence and country of origin of the mutation R496H.
abstract: BACKGROUND
  Gaucher disease is the most prevalent inherited disorder among Ashkenazi Jews (carrier frequency of about 6%) and six mutations account for about 96% of their mutant alleles. Two mutations, N370S and R496H, have been reported only in mildly affected or asymptomatic patients. Due to the rarity of R496H, it was recommended that it be excluded from screening programs.
  
  
  OBJECTIVE
  To verify the frequency and trace the origin of Gaucher mutations in screened individuals whose Ashkenazi ethnicity was confirmed by the birthplace of their grandparents.
  
  
  METHODS
  We conducted a retrospective analysis of the screened results for the period 2006-2011. Mutations were identified by restriction analysis, Tag-It detection system, Pronto diagnostic kit and Nanogen technology (NanoChip 400).
  
  
  RESULTS
  The heterozygote frequency of eight mutations was estimated in a cohort of 16,910 alleles. Two mutations, N370S and R496H, were the most frequent in our population. However, while the occurrence of N370S carriers was similar to other reports (1:19.4), that of R496H carriers was considerably elevated (1:207). Examination of the screened individuals' ethnicity showed a significant difference in the distribution pattern of the country of origin between the carriers of these two mutations.
  
  
  CONCLUSIONS
  The origin pattern differences between the two groups of heterozygotes might reflect a separate geographic region of introduction for various mutations. As a result, secondary subgroups could be formed within the Ashkenazi population. This might clarify the dissimilarities in the occurrence of R496H mutation reported by various centers.
authors.affiliation: Sheba Medical Center, Tel hashomer, Israel.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bronstein
authors.forename: Mazal
authors.initials: M
authors.lastname: Karpati
authors.forename: Leah
authors.initials: L
authors.lastname: Peleg
mesh_terms: D005260:Female; D005776:Gaucher Disease / Q000453:epidemiology / Q000235:genetics; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D015995:Prevalence; D012111:Residence Characteristics; D012189:Retrospective Studies
chemical_list: D005962:Glucosylceramidase