Dataset Information

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.

SUBMITTER: Macharia AW

PROVIDER: S-EPMC7336762 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Macharia Alexander W AW Mochamah George G Uyoga Sophie S Ndila Carolyne M CM Nyutu Gideon G Tendwa Metrine M Nyatichi Emily E Makale Johnstone J Ware Russell E RE Williams Thomas N TN

Molecular genetics & genomic medicine 20200511 7

<h4>Background</h4>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 A<sub>2</sub> (HbA<sub>2</sub> ) 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.<h4>Methods</h4>We used raised hemoglobin A<sub>2</sub> (HbA<sub>2</sub> ) values (> 4.0% of total Hb) to target all ...[more]

PMID: 32394645

Similar Datasets

Project description:BackgroundThe frequency of the beta-thalassemia (β-thalassemia) gene in Indonesia ranges from 3 to 10%. However, in the East Java province, there is still limited information on the prevalence of β-thalassemia mutations in clinically diagnosed beta-thalassemia patients of East Java. Therefore, this study aimed to characterize β-thalassemia mutations in selected patients in the East Java province of Indonesia.MethodsThis is an analytical observational study. Diagnosis of β-thalassemia was based on clinical presentation, complete blood count (CBC), and hemoglobin (Hb) electrophoresis. Blood specimens taken from each patient in three ethylenediaminetetraacetic acid (EDTA) tubes were analyzed for CBC and Hb electrophoresis and processed for DNA extraction and subsequent polymerase chain reaction (PCR). Detection of mutations in Hemoglobin Subunit Beta (HBB) gene exons 1-3 of the β-thalassemia gene as the common mutation in Indonesia was done using PCR followed by Sanger sequencing.ResultsIn total, 33 (n = 33) participants were involved in this study with ages ranging from 5 to 17 years comprising 19 women and 14 men. Their ethnic origins were Javanese (n = 30) and Chinese (n = 3). CBC results showed that mean ± standard deviation (SD) for Hb, red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW)-CV were 81.2 ± 7.0 g/L; 3.40 ± 0.39 × 109/L; 71.05 ± 5.72 fL; 24.12 ± 2.45 pg; 33.91 ± 1.47 g/dl; 24.38 ± 6.02%, respectively. Hb electrophoresis revealed that 5 out of 33 participants had beta-thalassemia and 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia. Results of Sanger sequencing showed the following genotype variations in the samples: 12 (36.4%) with β CD26 /β IVS-I-5; 6 (18.2%) with β CD26 /β CD35; 3 (9.1%) with β CD26 /β IVS-I-2; 2 (6.1%) with β CD27/28 /β CD40; 2 (6.1%) with β IVS-I-1 /β CAP+1; and β CD26 /β IVS-I-1; β IVS-I-5 /β CAP+1; β IVS-I-5 /β CD35; β CD26 /β CD37; β CD26 /β CD15; β CD26 /β CD40; and β IVS-I-5 /β CD19 in 1 (3%) sample, respectively, and 1 (3%) had no abnormality detected in sequencing even though electrophoresis showed abnormality in the migration pattern. The β CD26 /β IVS-I-5 mutation was found in samples that were noted to have Hb E/beta-thalassemia on Hb electrophoresis.ConclusionThe underlying genetic variations are heterogeneous in thalassemia patients in East Java, where 12 variants were found. The most common variant was β CD26 /β IVS-I-5, which all accounted for Hb E/beta-thalassemia on Hb electrophoresis. Furthermore, 28 out of 33 participants had hemoglobinopathy (Hb) E/beta-thalassemia.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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