title: Evaluation of the risk for Tay-Sachs disease in individuals of French Canadian ancestry living in new England.
abstract: BACKGROUND
  The assessment of risk for Tay-Sachs disease (TSD) in individuals of French Canadian background living in New England is an important health issue. In preliminary studies of the enzyme-defined carrier frequency for TSD among Franco-Americans in New England, we found frequencies (1:53) higher than predicted from the incidence of infantile TSD in this region. We have now further evaluated the risk for TSD in the Franco-American population of New England.
  
  
  METHODS
  Using a fluorescence-based assay for beta-hexosaminidase activity, we determined the carrier frequencies for TSD in 2783 Franco-Americans. DNA analysis was used to identify mutations causing enzyme deficiency in TSD carriers.
  
  
  RESULTS
  We determined the enzyme-defined carrier frequency for TSD as 1:65 (95% confidence interval 1:49 to 1:90). DNA-based analysis of 24 of the enzyme-defined carriers revealed 21 with sequence changes: 9 disease-causing, 4 benign, and 8 of unknown significance. Six of the unknowns were identified as c.748G>A p.G250S, a mutation we show by expression analysis to behave similarly to the previously described c.805G>A p.G269S adult-onset TSD mutation. This putative adult-onset TSD c.748G>A p.G250S mutation has a population frequency similar to the common 7.6 kb deletion mutation that occurs in persons of French Canadian ancestry.
  
  
  CONCLUSIONS
  We estimate the frequency of deleterious TSD alleles in Franco-Americans to be 1:73 (95% confidence interval 1:55 to 1:107). These data provide a more complete data base from which to formulate policy recommendations regarding TSD heterozygosity screening in individuals of French Canadian background.
authors.affiliation: Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Dianna C
authors.initials: DC
authors.lastname: Martin
authors.forename: Brian L
authors.initials: BL
authors.lastname: Mark
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Triggs-Raine
authors.forename: Marvin R
authors.initials: MR
authors.lastname: Natowicz
mesh_terms: D000328:Adult; D002170:Canada / Q000208:ethnology; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008404:Massachusetts / Q000453:epidemiology; D009154:Mutation; D012306:Risk; D013661:Tay-Sachs Disease / Q000208:ethnology* / Q000235:genetics*; D044465:White People; D054820:beta-Hexosaminidase alpha Chain; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics
chemical_list: C518253:HEXA protein, human; D054820:beta-Hexosaminidase alpha Chain; D001619:beta-N-Acetylhexosaminidases