Occurrence of common and rare δ-globin gene defects in two multiethnic populations: thirteen new mutations and the significance of δ-globin gene defects in β-thalassemia diagnostics

Summary Introduction: The aim of this review is to study the frequency of common and the occurrence of rare and novel mutations of the delta‐globin gene and of Hb Lepore defects that might interfere with thalassemia diagnostics and to report the rationale of HbA2 estimation in the presence of delta‐ or alpha‐gene mutations. Methods: A total of 135 cases suspected to have a delta‐globin gene defect collected in a diagnostic center in the USA and in a reference laboratory in the Netherlands were characterized by molecular analysis. Results: Hb B2 was found at a frequency of at least 0.5% in the USA and 0.87% in the Netherlands. Known variants such as Hb A2‐Babinga, Hb A2‐Sphakia, Hb A2‐Fitzroy, Hb A2‐Flatbush, Hb A2‐NYU, Hb A2‐Grovetown, HbA2‐Yialousa, Hb A2‐Indonesia and several delta‐thalassemia mutations were found together with 13 new mutations and two new polymorphisms, while Hb Lepores were regularly observed. Conclusion: HbA2 mutations either structurally stable and visible or undetectable because of a thalassemia effect or instability are clinically asymptomatic but may compromise the diagnosis of beta‐thalassemia minor. Stable mutations result in two HbA2 fractions of about half of the expected value. Expression defects are undetectable as a protein fraction but reduce the amount of HbA2 by half.