Molecular Basis of α-Thalassemia in Bahrain

Objectives: This study was designed to delineate the molecular lesions, on DNA level, that lead to α-thalassemia in the population of Bahrain. Methods: Various polymerase chain reaction (PCR)-based methodologies were involved, namely, differential PCR amplification, PCR-restriction fragment length polymorphism (PCR-RFLP), and direct PCR-amplified genomic DNA sequencing. Results: Five α-thalassemia determinants were identified. These include three deletional type, the rightward 3.7 kilobase (kb) deletion, the leftward 4.2 kb deletion, and the pentanucleotide deletion in 5 ' splice donor side of intron I in α2-globin gene (GGTGAGG→GG-----), and two nondeletional α-thal determinants, the Saudi type polyadenylation (polyA) signal mutation in the α2-globin gene (AATAAA→AATAAG), and the Turkish type polyA signal mutation (AATAAA→AATGAA), also in α2-globin gene. Conclusion: Three α-thalassemia mutations, the Saudi type polyA signal mutation, the pentanucleotide deletion and the rightward 3.7 kb deletion, account for 97 % of all α-thalassemia determinants in Bahrain. Recommendations: A well-tailored genetic counseling approach, supported by molecular studies, is advised for family members affected with α-thalassemia, and in particular for carriers of the polyA signal mutations