β-Thalassemia pathogenic variants in a cohort of children from the East African coast

Abstract

Background: β-Thalassemia is rare in sub-Saharan Africa. Previous studies have suggested that it is limited to specific parts of West Africa. Based on hemoglobin A₂ (HbA₂ ) concentrations measured by HPLC, we recently speculated that β-thalassemia might also be present on the East African coast of Kenya. Here, we follow this up using molecular methods.

Methods: We used raised hemoglobin A₂ (HbA₂ ) values (> 4.0% of total Hb) to target all HbAA members of a cohort study in Kilifi, Kenya, for HBB sequencing for β-thalassemia (n = 99) together with a sample of HbAA subjects with lower HbA₂ levels. Because HbA₂ values are artifactually raised in subjects carrying sickle hemoglobin (HbS) we sequenced all participants with an HPLC pattern showing HbS without HbA (n = 116) and a sample with a pattern showing both HbA and HbS.

Results: Overall, we identified 83 carriers of four separate β-thalassemia pathogenic variants: three β⁰ -thalassemia [CD22 (GAA→TAA), initiation codon (ATG→ACG), and IVS1-3' end del 25bp] and one β⁺ -thalassemia pathogenic variants (IVS-I-110 (G→A)). We estimated the minimum allele frequency of all variants combined within the study population at 0.3%.

Conclusions: β-Thalassemia is present in Kilifi, Kenya, an observation that has implications for the diagnosis and clinical care of children from the East Africa region.

Keywords: Kenya; Thalassemia; hematology; hemoglobinopathy.

Figure 1

Sample selection and sequencing results for identification of β‐thalassemia pathogenic variants in participants with different HbS phenotypes. Note: Total number of study participants were 15,577 distributed as (a) HbAA = 13,085 (84.0%); (b) HbAS = 2,366 (15.2%), and (c) HbSS = 126 (0.8%)