A New Mutation, Hb A₂-Canakkale [δ10(A7)Ala→Val; HBD: c.32C>T], and Other Well-Known δ Variants Identified in a Selected Cohort with Low Hb A₂ Levels

Abstract

Hemoglobinopathies are the most common single-gene disorders, and β-thalassemia (β-thal) imposes a tremendous health burden on Turkey. Thus, premarital carrier screening is obligatory in Turkey, as it is in some other countries. As a result of this mandatory procedure, at routine clinical checkups, many individuals who had undergone premarital screening but did not have any clinical symptoms and/or hematological findings, have compulsorily been required to undergo further evaluation due to abnormal levels of hemoglobin (Hb) fractions (Hb A, Hb A₂ and Hb F). Many consequences, such as mutations in unrelated gene(s) or someone’s nutritional status, have been reported to affect the Hb fractions levels. In the present study, we aimed to determine whether HBD has a molecular causative role in patients with low Hb A₂ levels (below 1.8%). The study was conducted with 20 individuals with low Hb A₂ levels who had applied to our outpatient clinic. All DNA samples were analyzed for the HBD gene. Nineteen of the 20 subjects were diagnosed to carry a mutation with one of four different δ-globin variants. Three of them had been described previously [Hb A₂-Yialousa (HBD: c.82G>T), Hb A₂-Bornova (HBD: c.350G>C) and Hb A₂-Yokoshima (HBD: c.77G>A)]. The novel [δ10(A7)Ala→Val, HBD: c.32C>T] mutation was defined as a new δ variant and reported to the HbVar database as Hb A₂-Canakkale. In conclusion, the molecular characterization of Hb A₂ low levels has been suggested to be significant for a definite diagnosis and counseling.

Keywords:

• δ-Thalassemia (δ-thal)
• HBD
• low Hb A₂ level

Acknowledgements

We would like thank all the study subjects for their participation and collaboration.

Disclosure statement

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