title: Molecular basis of hexosaminidase A deficiency and pseudodeficiency in the Berks County Pennsylvania Dutch.
abstract: Following the birth of two infants with Tay-Sachs disease (TSD), a non-Jewish, Pennsylvania Dutch kindred was screened for TSD carriers using the biochemical assay. A high frequency of individuals who appeared to be TSD heterozygotes was detected (Kelly et al., 1975). Clinical and biochemical evidence suggested that the increased carrier frequency was due to at least two altered alleles for the hexosaminidase A alpha-subunit. We now report two mutant alleles in this Pennsylvania Dutch kindred, and one polymorphism. One allele, reported originally in a French TSD patient (Akli et al., 1991), is a GT-->AT transition at the donor splice-site of intron 9. The second, a C-->T transition at nucleotide 739 (Arg247Trp), has been shown by Triggs-Raine et al. (1992) to be a clinically benign "pseudodeficient" allele associated with reduced enzyme activity against artificial substrate. Finally, a polymorphism [G-->A (759)], which leaves valine at codon 253 unchanged, is described.
authors.affiliation: Genetics Laboratory, Kennedy Krieger Institute, Baltimore, Maryland 21205.
authors.forename: E H
authors.initials: EH
authors.lastname: Mules
authors.forename: S
authors.initials: S
authors.lastname: Hayflick
authors.forename: C E
authors.initials: CE
authors.lastname: Dowling
authors.forename: T E
authors.initials: TE
authors.lastname: Kelly
authors.forename: B R
authors.initials: BR
authors.lastname: Akerman
authors.forename: R A
authors.initials: RA
authors.lastname: Gravel
authors.forename: G H
authors.initials: GH
authors.lastname: Thomas
mesh_terms: D000483:Alleles; D001483:Base Sequence; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity; D005260:Female; D006580:Genetic Carrier Screening; D054818:Hexosaminidase A; D006801:Humans; D008297:Male; D010375:Pedigree; D010414:Pennsylvania; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013661:Tay-Sachs Disease / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000172:deficiency* / Q000235:genetics*
chemical_list: D004247:DNA; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases