Various α-Thalassemia Genotype Combinations of the Saudi-Type Polyadenylation Signal Mutation (αT-Saudiα) in the Population of Bahrain: An Update of Genotype-Phenotype Analyses

Abstract

The Saudi-type polyadenylation (polyA) signal mutation on the α2-globin gene, HBA2: c.*94A > G; AATAAA>AATAAG; αT-Saudiα, is one of the major α-thalassemia (α-thal) determinants in the population of Bahrain. We determined five different genotype combinations involving this mutation in Bahrain. Here, we report these various genotypes involving the Saudi-type polyA signal mutation and their relevant phenotype presentations. A total of 32 patients were diagnosed with the genotype of αT-Saudiα/αT-Saudiα. These homozygous patients presented with a typical form of Hb H disease and severe anemia with a mean hemoglobin (Hb) level of 8.5 ± 0.7 g/dL. Second, we diagnosed 29 patients carrying the genotype of αT-Saudiα/αHpHα, and they presented with a less severe form of Hb H disease and a mean Hb level of 9.9 ± 0.9 g/dL. Third, we found two genotype combinations of the polyA signal mutation with either the rightward (–α3.7) (n = 46) or leftward (–α4.2) (n = 22) deletions. These patients presented with an α-thal trait phenotype or a mild form of Hb H disease with a mean Hb level of 10.8 ± 1.0 g/dL for the –α3.7/αT-Saudiα, and 10.4 ± 1.4 g/dL for the –α4.2/αT-Saudiα genotypes. We also found 39 patients with the simple heterozygous state of the polyA signal mutation, who presented with a mild form of α-thal trait and a mean Hb level of 12.1 ± 1.7 g/dL. Finally, data from 48 patients carrying the normal α genotype (αα/αα) are presented with a mean Hb level of 12.9 ± 1.7 g/dL. These data could pave the way for accurate genetic counseling and sound clinical management based on precise molecular diagnosis of α-thal.