title: Tay-Sachs disease in Moroccan Jews: deletion of a phenylalanine in the alpha-subunit of beta-hexosaminidase.
abstract: Tay-Sachs disease is an inherited lysosomal storage disorder caused by defects in the beta-hexosaminidase alpha-subunit gene. The carrier frequency for Tay-Sachs disease is significantly elevated in both the Ashkenazi Jewish and Moroccan Jewish populations but not in other Jewish groups. We have found that the mutations underlying Tay-Sachs disease in Ashkenazi and Moroccan Jews are different. Analysis of a Moroccan Jewish Tay-Sachs patient had revealed an in-frame deletion (delta F) of one of the two adjacent phenylalanine codons that are present at positions 304 and 305 in the alpha-subunit sequence. The mutation impairs the subunit assembly of beta-hexosaminidase A, resulting in an absence of enzyme activity. The Moroccan patient was found also to carry, in the other alpha-subunit allele, a different, and as yet unidentified, mutation which causes a deficit of mRNA. Analysis of obligate carriers from six unrelated Moroccan Jewish families showed that three harbor the delta F mutation, raising the possibility that this defect may be a prevalent mutation in this ethnic group.
authors.affiliation: Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: R
authors.initials: R
authors.lastname: Navon
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002478:Cells, Cultured; D003062:Codon; D004247:DNA / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007585:Jews; D008969:Molecular Sequence Data; D009018:Morocco / Q000208:ethnology; D009154:Mutation; D015345:Oligonucleotide Probes; D010649:Phenylalanine / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D013661:Tay-Sachs Disease / Q000453:epidemiology* / Q000235:genetics; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D003062:Codon; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D010649:Phenylalanine; D004247:DNA; D001619:beta-N-Acetylhexosaminidases