# The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience

## TL;DR

This study explores a rare genetic variant in Malaysia that causes significant alpha-thalassemia and highlights its clinical importance.

## Contribution

The study identifies and characterizes a rare α2-globin gene variant (AATA(--AA)) in the Malaysian population and its clinical impact.

## Key findings

- 32 patients with AATA(--AA) showed a thalassemia-like phenotype, including carriers and compound heterozygotes.
- Compound cases with AATA(--AA) and other α-thalassemia variants showed moderate to severe symptoms.
- AATA(--AA) homozygotes and combinations with Hb Adana, Hb CS, and Hb Pakse were identified.

## Abstract

Poly A (AATAAA > AATA--) [HBA2:c.*93_*94delAA] is a rare α-variant reported in our population. It is caused by 2 bp deletion (--AA) in the α2 poly A sequence, leading to a significant α–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 α-thalassaemia in a five-year period. Alpha-Gap and ARMS-PCR were performed to detect common α-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 α–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 α-variant exhibited a significant phenotype between moderate to severe thalassaemia, especially cases with compound α−AAα/αAdanaα. Conclusions: AATA(--AA) is a significant pathogenic variant that should be diagnosed to prevent significant thalassaemia phenotype or transfusion-dependent thalassaemia.