Alpha Thalassemia Genotypes in Kuwait
Abstract Background: The frequency of alpha thalassemia trait is about 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of the patients who were referred for molecular diagnosis over a 20-year period. Methods: This is a retrospective study of the a-globin genotypes obtained in the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University from 1994 to 2015. Genotyping was by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot-blot hybridization (Vienna Lab Strip Assay). Results: Four hundred samples were characterized and analyzed from individuals aged <1 month to 80 years, with a median of 6 years from 283 unrelated families.. Most (90.8%) were Kuwaiti nationals. The common genotype was homozygosity for the polyadenylation-1 mutation (α PA-1 α/α PA-1 α) in 33.3%, followed by heterozygosity (αα/α PA-1 α) for the same mutation in 32.3%. The PA-1 was therefore the most frequent allele (0.59). The frequency of the α 0 , – MED was 0.017. Rare alleles that were found in very low frequencies included the α 0 (-- FIL ) in a Filipino child, Hb Constant Spring, Hb Adana, and Hb Icaria. Conclusion : There is a wide variety of alpha thalassemia alleles among Kuwaitis, but the nondeletional PA-1 is by far the most common cause of moderate to severe HbH (β4 tetramer), disease phenotype. The α 0 (– MED ) allele is also encountered, which has implications for pre-marital counselling especially the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).