Abstract
BackgroundThe frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of patients who were referred for molecular diagnosis over a 20-year period.MethodsThis is a retrospective study of the α-globin genotypes obtained in the Hemoglobin Research Laboratory of the Department of Pediatrics, Kuwait University from 1994 to 2015. Genotyping was performed by a combination of PCR, allele-specific oligonucleotide hybridization and reverse dot blot hybridization (Vienna Lab Strip Assay).ResultsFour 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 commonest genotype was homozygosity for the polyadenylation-1 mutation (αPA-1α/α PA-1α) in 33.3% of the samples, followed by heterozygosity (αα/α PA-1α) for the same mutation in 32.3%. PA-1 was therefore the most frequent allele (0.59). The frequency of the α0 (−-MED) allele was 0.017. Rare alleles that were found in very low frequencies included α0 (−-FIL) in a Filipino child, Hb Constant Spring, Hb Adana, and Hb Icaria.ConclusionThere is a wide variety of alpha thalassemia alleles among Kuwaitis, but nondeletional PA-1 is by far the most common cause of the moderate to severe HbH (β4 tetramer) disease phenotype. The α0 (−MED) allele is also encountered, which has implications for premarital counseling, especially for the possibility of having babies with alpha thalassemia major (Barts hydrops fetalis).
Highlights
The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles
Four hundred blood samples were received with the diagnosis of suspected moderate to severe alpha thalassemia or HbH disease over the period of the study from 1994 to 2015
The most common (33.3%) was homozygosity for αPA-1 (c.*94A > G) nondeletional α-thal allele, which gives an HbH disease phenotype, followed by
Summary
The frequency of the alpha thalassemia trait is approximately 40% in the Kuwaiti population, but there has been no comprehensive study of the prevalent alleles. This is a report of patients who were referred for molecular diagnosis over a 20-year period. The normal individual has a complement of four αglobin genes (αα/αα), any one of which can be absent, producing varying degrees of alpha thalassemia [1]. One- or 2gene deletions (−α/αα, −α/−α, −−/αα) produce the α-thal trait, which is usually associated with mild microcytic and hypochromic anemia. The loss of 3 genes (−−/−α) produces classical hemoglobin H (HbH, β4 tetramer) disease, which is characterized by moderate to severe anemia. The loss of all 4 genes (−−/−−) causes Hb Barts (γ4) hydrops fetalis, which is incompatible with life in the absence of the early onset of chronic transfusion or stem cell transplantation [6]
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