title: The molecular basis of HEXA mRNA deficiency caused by the most common Tay-Sachs disease mutation.
abstract: Tay-Sachs disease (TSD) is a catastrophic neurodegenerative disorder caused by mutations in the HEXA gene. The most common TSD allele worldwide contains a 4-bp insertion in exon 11 that produces a downstream premature termination codon. Despite normal transcription of this allele, HEXA mRNA is severely reduced, indicating that the HEXA transcript must be unstable. Minigenes of HEXA were constructed and expressed in mouse L cells, to investigate the relationship between the 4-bp insertion and mRNA deficiency. We conclude that the mRNA instability is caused by the premature termination codon and not by a cryptic mutation or by the 4-bp insertion directly and that degradation occurs coincident with or after splicing.
authors.affiliation: Section on Biochemical Genetics, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20892-1810.
authors.forename: D J
authors.initials: DJ
authors.lastname: Boles
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005091:Exons; D054818:Hexosaminidase A; D006801:Humans; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis*; D013661:Tay-Sachs Disease / Q000235:genetics*; D014162:Transfection; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases