title: A novel exon mutation in the human beta-hexosaminidase beta subunit gene affects 3' splice site selection.
abstract: The molecular basis of a dramatically decreased steady state level of beta-hexosaminidase beta subunit mRNA in a patient with juvenile Sandhoff disease was investigated. Nucleotide sequence analysis of the HEXB gene coding for the beta subunit revealed two single base substitutions, one in exon 2 (A to G, a known polymorphism) and the other in exon 11 (C to T). Analysis of the beta subunit mRNA species demonstrated activation of a cryptic splice site in exon 11 as well as skipping of the exon. A transfection assay using a chimeric gene containing intron 10 flanked by cDNA sequences carrying the mutation confirmed that the single base substitution located at position 8 of exon 11 inhibits the selection of the normal 3' splice site. The results demonstrate a new type of exon mutation affecting 3' splice site selection.
authors.affiliation: Department of Neurology, Niigata University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Wakamatsu
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Miyatake
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D000328:Adult; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D002678:Chimera; D004247:DNA / Q000235:genetics; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism; D054819:Hexosaminidase B; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012497:Sandhoff Disease / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D004247:DNA; D054819:Hexosaminidase B; D001619:beta-N-Acetylhexosaminidases