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.
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: Hans Thomas Hölzer; Felix Boschann; Julia B Hennermann; Gabriele Hahn; Andreas Hermann; Maja von der Hagen; Victoria Tüngler Journal: J Neurol Date: 2021-03-09 Impact factor: 4.849
Authors: Alana C Cecchi; Elizabeth S Vengoechea; Kristjan E Kaseniit; Melanie W Hardy; Laura A Kiger; Nikita Mehta; Imran S Haque; Krista Moyer; Patricia Z Page; Dale Muzzey; Karen A Grinzaid Journal: Mol Genet Genomic Med Date: 2019-07-10 Impact factor: 2.183
Authors: Jodi D Hoffman; Valerie Greger; Erin T Strovel; Miriam G Blitzer; Mark A Umbarger; Caleb Kennedy; Brian Bishop; Patrick Saunders; Gregory J Porreca; Jaclyn Schienda; Jocelyn Davie; Stephanie Hallam; Charles Towne Journal: Mol Genet Genomic Med Date: 2013-09-16 Impact factor: 2.183
Authors: Nikita Mehta; Gabriel A Lazarin; Erica Spiegel; Kathleen Berentsen; Kelly Brennan; Jessica Giordano; Imran S Haque; Ronald Wapner Journal: Genet Test Mol Biomarkers Date: 2016-06-30