title: A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients.
abstract: Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G----T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration.
authors.affiliation: Genetics Laboratory, Kennedy Institute, Baltimore, MD 21205.
authors.forename: E H
authors.initials: EH
authors.lastname: Mules
authors.forename: C E
authors.initials: CE
authors.lastname: Dowling
authors.forename: M B
authors.initials: MB
authors.lastname: Petersen
authors.forename: H H
authors.initials: HH
authors.lastname: Kazazian
authors.forename: G H
authors.initials: GH
authors.lastname: Thomas
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D004247:DNA / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D013661:Tay-Sachs Disease / Q000235:genetics*; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D004247:DNA; D001619:beta-N-Acetylhexosaminidases