BACKGROUND AND OBJECTIVES:
α-Thalassemia is a microcytic anemia characterized by the downregulation of α-globin synthesis. Premature destruction of red blood cells in the bone marrow ensues, resulting in deficient erythropoiesis. Mutations in the globin gene resulting in quantitative or structural changes in the globin chain can be caused by sequence variations, deletions of ≥1 of the structural genes, and deletions extending beyond the globin cluster. The frequency and types of α-thalassemia mutation among children and adolescents in the state of Qatar are not known. The objectives were to study the molecular basis of the α-thalassemia gene among Qatari children and adolescents to determine the frequency and types of α-thalassemia mutations in the pediatric population.
Qatari children between the ages of 5 and 15 years exhibiting laboratory findings suggestive of microcytic anemia were pooled from Qatari public schools. Those with a hemoglobin of <12 g/dL, a mean corpuscular volume of <80 fL, iron studies within the normal range, and a hemoglobin electrophoresis that ruled out α-thalassemia were narrowed down to a group of 150 children and adolescents with suspected α-thalassemia. The patients were screened for deletions in −α3.7, the most common α-thalassemia deletion. Subsequent screenings for deletions in α-5nt, α-poly-A1 (α-T-Saudi), and α-poly-A2, α-thalassemia deletions prevalent in neighboring Middle Eastern countries, was also performed.
Of the anemic subjects, 37.9% tested positive for the −α3.7 deletion, 4.5% tested positive for the α-poly-A1 deletion, and 1.5% tested positive for the α-5nt mutation. None of the children exhibited any changes in α-poly-A2. We also tested 59 samples that revealed no mutations initially. Among 59 samples, 43 showed normal sequencing for α1 and α2 and 16 showed no result. So we did multiplex ligation-dependent probe amplification for these 16 samples: 2 samples showed compound heterozygous (HT-RW) and (HT-20.5) (12.5%), 2 samples showed compound heterozygous (HT-RW) and (HT-20.5) (12.5%), and 2 samples showed African polymorphism (12.5%).
Our results suggest that a significant number of the Qatari pediatric population exhibits mutational changes responsible for the increasing prevalence of α-thalassemia in the population. Of the children pooled, 48% exhibited mutations suggestive of α-thalassemia. This suggests the possibility of other existing mutations in the Qatari pediatric population that are yet to be elicited. Additional testing of the 59 samples revealed new mutations. We are exploring new mutations of α-thalassemia in the Qatari population.
- Copyright © 2015 by the American Academy of Pediatrics