title: Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene.
abstract: We have identified two novel RNA-splicing mutations affecting a critical nucleotide (nt) in the acceptor consensus sequences at both the IVS-1/exon 2 and IVS-2/exon 3 junctions of the human beta-globin gene. Both mutations are single nt substitutions, T to G and C to A, at position -3 adjacent to the invariant AG dinucleotide. For the IVS-2/exon 3 mutation abnormal splicing into the cryptic splice site at IVS-2 nt 579 is documented. Identification of these two mutations provides further support for the importance of the location of specific nucleotides within the consensus sequences in splice site selection and RNA processing.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: S C
authors.initials: SC
authors.lastname: Goff
authors.forename: S H
authors.initials: SH
authors.lastname: Orkin
authors.forename: B G
authors.initials: BG
authors.lastname: Forget
authors.forename: D G
authors.initials: DG
authors.lastname: Nathan
authors.forename: P J
authors.initials: PJ
authors.lastname: Giardina
authors.forename: H H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D001483:Base Sequence; D005091:Exons; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D013789:Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins