title: Human alpha2-globin nonsense-mediated mRNA decay induced by a novel alpha-thalassaemia frameshift mutation at codon 22.
abstract: We describe a novel alpha-thalassaemia determinant in a 3-year-old girl presenting a mild microcytic and hypochromic anaemia, and normal haemoglobin A2 level. Molecular studies revealed heterozygosity for a novel microdeletion (-C) at codon 22 of the alpha2-globin gene. As the frameshift mutation generates a premature translation termination codon at position 48/49, we investigated the effect of the nonsense codon on the alpha2-globin gene expression. Although it does not affect RNA splicing, the premature nonsense codon induces accelerated mRNA degradation. To our knowledge, this is the first time the nonsense-mediated mRNA decay has been reported to occur in human alpha-globin mRNA.
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal.
authors.forename: Francisco J C
authors.initials: FJ
authors.lastname: Pereira
authors.forename: Maria
authors.initials: M
authors.lastname: do Céu Silva
authors.forename: Isabel
authors.initials: I
authors.lastname: Picanço
authors.forename: Maria T
authors.initials: MT
authors.lastname: Seixas
authors.forename: Anabela
authors.initials: A
authors.lastname: Ferrão
authors.forename: Paula
authors.initials: P
authors.lastname: Faustino
authors.forename: Luísa
authors.initials: L
authors.lastname: Romão
mesh_terms: D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D015870:Gene Expression; D005822:Genetic Vectors / Q000494:pharmacology; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger; D005914:Globins