First Case of Hb City of Hope (HBB: c.208G > A) in Andalusia. A Molecular Update of β-Thalassemia in Southwestern Spain (Huelva Province)

Abstract

Beta-thalassemia, caused by mutations in the β-globin gene, is an important disease for both basic and translational research. This hemoglobinopathy is molecularly and clinically heterogeneous, and its high prevalence in certain geographic areas has been attributed to a combination of evolutionary, environmental, and sociocultural factors. This report provides an update on the genetic dissection of β-thalassemia in western Andalusia (southern Spain) using a population genetics approach. The results were consistent with previous reports and support the idea of a specific substrate for the disorder in southwestern Iberia, with variant IVS I-1 (G > A) being a hallmark of autochthonous people. A single case of the hemoglobin variant Hb City of Hope (CD 69), a rare mutation reported in fewer than fifty individuals worldwide, was detected. Clinical differences associated with the specific β-globin mutation were also explored, with significance observed only for MCV when comparing mean values of IVS II-745 vs. CD 39 and IVS II-745 vs. IVS I-1.