The clinical and laboratory profiles of a deletional α2-Globin gene polyadenylation signal sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: the Malaysian Experience

Abstract

Poly A (AATAAA > AATA--) [HBA2:c.*93_*94delAA] is a rare alpha-variant reported in our population. It is caused by 2 bp deletion (--AA) in the alpha 2 poly A sequence, leading to a significant alpha-thalassaemia phenotype.

Background/Objectives: This study describes the haematological parameters, phenotype, and genotype characteristics of AATA(--AA) in the Malaysian population.

Methods: The study was carried out on 17 177 cases referred to the Institute for Medical Research, Malaysia, for further diagnosis of alpha-thalassaemia in a five-year period. Alpha-Gap and ARMS-PCR were performed to detect common alpha-thalassaemia, followed by HBA1 and HBA2 genes sequencing and multiplex ligation-dependent probe amplification (MLPA). Haematological parameters among various groups with the AATA(--AA) allele were presented in this study. Results: Thirty-two patients with AATA(--AA) displaying an alpha-thalassaemia-like phenotype were analysed. They comprised 22 (68.75%) AATA(--AA) carriers, 2 (6.25%) compounds with 3.7 deletion, 2 (6.25%) compounds with --SEA deletion, 1 (3.12%) AATA(--AA) homozygote, and 3 (9.37%) compounds of Hb Adana, Hb CS, and Hb Pakse with co-inheritance Hb E, respectively. Most of the patients with AATA(--AA) compounds with the alpha-variant exhibited a significant phenotype between moderate to severe thalassaemia, especially cases with compound alpha(-AA)alpha/alpha(Adana)alpha. Conclusions: AATA(--AA) is a significant pathogenic variant that should be diagnosed to prevent significant thalassaemia phenotype or transfusion-dependent thalassaemia.