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Human α 2‐globin nonsense‐mediated mRNA decay induced by a novel α ‐thalassaemia frameshift mutation at codon 22
Author(s) -
Pereira Francisco J. C.,
Silva Maria do Céu,
Picanço Isabel,
Seixas Maria T.,
Ferrão Anabela,
Faustino Paula,
Romão Luísa
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.05971.x
Subject(s) - frameshift mutation , nonsense mediated decay , nonsense mutation , messenger rna , genetics , rna splicing , nonsense , biology , microbiology and biotechnology , mutation , globin , gene , stop codon , translation (biology) , loss of heterozygosity , rna , allele , missense mutation
Summary We describe a novel α ‐thalassaemia determinant in a 3‐year‐old girl presenting a mild microcytic and hypochromic anaemia, and normal haemoglobin A 2 level. Molecular studies revealed heterozygosity for a novel microdeletion (−C) at codon 22 of the α 2 ‐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 α 2 ‐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 α ‐globin mRNA.