Nondeletional α-Thalassemia: Two New Mutations on the α2 Gene

Abstract

About 10.0% of α-thalassemia (α-thal) cases are due to point mutations, small deletions, or insertions of one or more bases on the α genes that can alter mRNA processing at the transcription, translation, or post-translation level; these cases are called nondeletional α-thalassemias (α-thal). Most occur within the domain of the α2 gene without changes in the expression of the α1 gene. We present two new frameshift mutations on the HBA2 gene, associated with a nondeletional α-thal phenotype. The probands were referred to our clinic because of persistent microcytosis and hypochromia. The molecular characterization was performed by automatic sequencing of the α-globin genes. Two new mutations were detected on the HBA2 gene; HBA2: c.85delG, p.(Ala29fs*21), and HBA2: c.268_280delCACAAGCTTCGGG, p.(His90Trpfs*9). These new mutations cause a change of the reading frame, the first on codon 28 and the second from codons 89 to 93. In the first mutation, the result is an altered amino acid sequence and a premature termination codon at position 87, while the elimination of 13 bp generates a protein of 95 residues and in this case, the premature termination codon is at position 96. These types of mutation are among the most damaging changes to the coding of a protein. Not only do they lead to changes in the length of the polypeptide, but they also vary the chemical composition, which would result in a nonfunctional protein. The importance of identifying these new mutations lies in their possible association with α⁰-thal, which could lead to a severe thalassemia.

Keywords:

• α-Thalassemias
• HBA2 gene
• nondeletional

Author contributions

A. Villegas, C. Benavente, F.A. González and P. Ropero conceived this case report; J. Arbetera provided the clinical data of the studied patient; P. Ropero, J.M. Nieto and B. González performed the molecular studies and conducted genetic analyses; P. Ropero prepared the manuscript. All authors discussed the results and implications and commented on the manuscript at all stages.

Acknowledgements

The authors would like to thank the great help that Mrs. Marianne F. H. Carver has lent us in the edition of this manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.