Molecular and Hematological Characterization of a Novel Translation Initiation Codon Mutation of the α2-Globin Gene (AT>AT or : c.3G>C).

Although mutations causing α-thalassemia (α-thal) are mainly larger deletions involving one or both of the duplicated α-globin genes, point mutations are not rare. We have identified a novel mutation of the translation initiation codon of the α2-globin gene with DNA sequencing and allele-specific multiplex ligation-dependent probe amplification (MLPA) in a Chinese family. RNA analysis was performed with reverse transcription-MLPA (RT-MLPA). A novel mutation at the translation initiation codon of the α2-globin gene (: c.3G>C) was identified. The proband and his father, who were both carriers of this mutation, had a hematological phenotype of mild α-thalassemia (α-thal) trait with low-normal limit of mean corpuscular volume (MCV) and normal Hb A. RNA analysis showed markedly decreased levels of α-globin mRNA and the presence of a small amount of mutant mRNA. The : c.3G>C mutation most likely caused α-thal by lowering levels of wild α-globin chain. Our study increases the mutation spectrum of α-thal.