Molecular and hematological studies in a cohort of beta zero South East Asia deletion (beta degrees-thal SEA) from Malaysian perspective

We report the haematological parameters and molecular characterization of beta zero (beta degrees) South East Asia (SEA) deletion in the HBB gene cluster with unusually high levels of Hb F compared to a classical heterozygous beta zero (beta degrees)-thalassaemia.Methods: Retrospective study on 17 cases of (beta degrees) South East Asia (SEA) deletion from 2016 to 2019 referred to Institute for Medical Research were conducted. The clinical information and haematological profiles were evaluated. The mutation was analyzed, and the results were compared with other beta degrees-thalassaemia groups. For HBB gene genotyping, all the cases were subjected for multiplex gap-PCR, 5 cases were subjected for HBB gene sequencing for exclusion of compound heterozygous with other beta variants. Co-inheritance of alpha-thalassaemia were determined using multiplex gap-PCR and multiplex ARMS-PCR.Results: Seventeen cases were positive for beta degrees-thal SEA deletion. Fifteen cases were heterozygous and two were compound heterozygous for beta degrees-thal SEA deletion. The results were compared with 182 cases of various heterozygous beta degrees deletions and mutations. The mean Hb for heterozygous beta degrees-thal SEA deletion (13.44 +/- 1.45 g/dl) was normal and significantly higher than heterozygous IVS 1-1 and Codon 41/42 (post hoc test, p < 0.05). The medians for the MCV and MCH of beta degrees-thal SEA deletion were significantly higher than for all heterozygote beta degrees-thalassaemia traits (Mann Whitney test, p < 0.05). Patients with beta degrees-thal SEA deletion had elevated levels of Hb A2 consistent with beta-thalassaemia traits, with Hb F levels consistent with HPFH or delta beta-thalassaemia carriers. The median for Hb A2 was 4.00 + 1.00%, similar to that observed in other beta degrees-thalassaemia groups except for IVS 1-1 mutation (median 5.30 + 0.45%) and beta degrees-Filipino (similar to 45 kb deletion) deletion (median 6.00 + 0.58). Interestingly, we found that Hb F levels for beta degrees-thal SEA deletion were statistically higher than other beta degrees-thalassaemia mutations (median 19.00 + 5.50%, p < 0.05), except for the beta degrees-thal 3.5 kb deletion group.Conclusion: We conclude that beta degrees-thal SEA deletion has a unique haematological parameters of beta zero thalassaemia trait. We affirm to classifying this deletion as SEA-HPFH based on previous studies considering the phenotype features rather than the moleculardefect of beta degrees-thal SEA deletion, as this will make it easier to offer genetic counselling to affected individuals.