Coinheritance of Beta Thalassaemia (β0 Filipino) and Delta Variant (HbA2 Deventer) in Sabahan Population: A Case Series

Abstract

Mutations in the δ globin gene are not pathologically significant [1]. However, coinheritance of β and δ thalassaemia can mask the diagnosis of β thalassaemia trait as it causes HbA₂ level to be lowered [2,3]. Here, we reported 5 unrelated cases of compound heterozygous β⁰ Filipino ~ 45 kb deletion and codon 67 (GTG>ATG) HbA2 Deventer in Sabahan population.

Cases of β°-thalassemia traits with unusual low HbA₂ were reviewed. These cases were initially referred to our laboratory for definitive diagnosis of β-thalassemia trait. Haematological parameters and Hb analysis were carried out at the referral hospital. Genomic DNA was extracted from the peripheral blood. Multiplex ARMS and Gap PCR were done to detect common point mutations and deletions for both alpha and beta globin genes. Sanger sequencing was performed to detect mutations in delta globin gene.

Patients’ consist of 4 males and 1 female aged between 25-38 years old. All of them are indigenous Sabahan (2 Kadazans, 1 Murut, 1 Dusun and 1 Sungai). Their haemoglobin level ranges between 10.8 – 12.8g/dl. Hb analysis findings of HbA₂ and HbF level ranges between 2.9 – 4.0 and 2.2 – 9.4g/dl respectively. Molecular findings revealed heterozygous state of (β)º-thal, Filipino ~45Kb deletion, NG_000007.3:g.[66258_184734del];[66258_184734=] and heterozygous state of Codon 67 [GTG>ATG] Hb A₂-Deventer mutation, NG_000007.3:g.[63512G>A];[63512G=] (Figure 1 and 2).

Detection of 5 unrelated cases of HbA₂ Deventer may suggest that this delta variant is common among indigenous Sabahan. Since beta thalassaemia is also common in the population, more attention should be paid during diagnosis. Identification of delta variant in beta thalassaemia carrier is important because coinheritance of beta and delta thalassaemia results in a less elevated HbA2 level. Therefore, molecular testing of thalassemia carrier state in the case of borderline HbA₂ is warranted to avoid misdiagnosis of beta thalassaemia carriers.