α-Thalassemia Syndromes in the United Arab Emirates

Abstract

α-Thalassemia (α-thal) is usually due to deletions within the α-globin gene cluster, leading to loss of function of one or both α-globin genes. α-Thalassemia is prevalent in the Arabian Peninsula, particularly in the United Arab Emirates (UAE) and Saudi Arabia. There are no large-scale reports regarding the prevalence of α-thal in the Arabian populations apart from sporadic surveys in the mid-1980s on red cell indices from Saudi Arabia and a more recent study from Kuwait. Several studies were conducted in an attempt to elucidate the frequency of α-thal in the UAE. Cord blood samples were collected from 419 consecutive newborns of UAE national mothers. The study involved polymerase chain reaction (PCR)-based analysis of the α-globin genes and sequencing using an ABI Genetic Analyser 3130. The findings demonstrated that 49% of the neonates had α-thal, one of the highest in the world. The incidence of α-thal, particularly the –α^3.7 deletion, was extremely high. The distribution of mutations was extensive, ranging from the simple –α^3.7 genotype to severe nondeletional type α-thalassemias such as the polyadenylation signal (polyA1) [α^PA–1 (AATAAA>AATAAG)], polyA2 [α^PA–2 (AATAAA>AATGAA)], Hb Constant Spring [Hb CS, α142 (α^CSα/α^CSα) TAA>CAA (α2)] and pentanucleotide deletion [α^{−5 nt} (GAGGTGAGG>GAGG)]. The nondeletional mutations, denoted α^Tα or αα^T, are markedly frequent in the UAE and are well characterized. The report here describes the analysis of 84 chromosomes having deletional and nondeletional types of α-thal. Of the 84 chromosomes, 47.4% had the polyA1 mutation (α^PA–1α), 28.2% had the small deletion –α^3.7, 11.5% had Hb CS (α^CSα), and 5% were positive for the pentanucleotide deletion (α^{−5 nt}α). These findings show that nondeletional α-thal has a significant impact on the genotype/phenotype correlation in the UAE. It is important to note that the polyA1 mutation accounted for almost 50% of all the α-thal alleles, making it one of the most common mutations in the Gulf Region.

• Deletional
• Nondeletional α-thalassemia (α-thal)
• Hb H disease
• α-Globin gene mutations
• United Arab Emirates (UAE)