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.
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References
Hariharan P., et al., Delta globin gene variations leading to reduction in HbA2 levels. International Journal of Laboratory Haematology, 2016. 38(6): p. 610-615.
Azam, A., et al., First report on the coinheritance of beta globin IVS 1-5 (G->C) Thalassaemia with Delta Globin CD12 {Asn->Lys(AAT->AAA)} HbA2-NYU in Iran. Archives of Iranian Medicine, 2011. 14(1): p. 8-11.
Bouva, M. J., et al., Known and new delta globin gene mutations and their diagnostic significance. Haematologica, 2006. 91(1): p. 129-132.
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