Molecular Characterization of α-Thalassemia in the Dohuk Region of Iraq

Abstract

The molecular basis of alpha-thalassemia (alpha-thal) has been addressed by several studies from the eastern Mediterranean region, but not from Iraq. To address this issue, we studied 51 individuals with unexplained hypochromia and/or microcytosis, as well as nine patients with documented Hb H disease from the Dohuk region in northern Iraq. We used multiplex gap-polymerase chain reaction (gap-PCR), reverse hybridization, and sequencing for this purpose. It was found that the most common genotypes in those with unexplained hypochromia and/or microcytosis were -alpha(3.7)/alpha alpha, followed by - -(MED-I)/alpha alpha, then -alpha(3.7)/-alpha (3.7), respectively, detected in 84.3% of the above individuals. Other genotypes identified sporadically were -alpha(4.2)/alpha alpha, alpha(poly A1)alpha/alpha alpha (AATAAA>AATAAG), alpha(Adana)alpha/alpha alpha [Hb Adana, codon 59 (Gly-->Asp) or HBA1:c.179G>A], and alpha(Evanston)alpha/alpha alpha [Hb Evanston, codon 14 (Trp-->Arg) or HBA1:c.43 T>C]. Three cases (5.88%) remained uncharacterized even after sequencing. All nine Hb H cases carried the -alpha(3.7)/- -(MED-I) genotype. Such findings are rather different from those in other eastern Mediterranean populations, particularly with relevance to an Hb H molecular basis.

Alpha-Thalassemia Mutations in Adana Province, Southern Turkey: Genotype-Phenotype Correlation

“…Gene deletions including -a 17.4 , -a 26.5 , -a 20.5 , a2 -5nt , -a 3.7 , and -a 4.2 , mutations including a2 -Poly A1 , a2 -Poly A2 and a1 cd 59 G [ A point mutation and aaa anti-3.7 gene triplication have been reported in several studies from our country and the frequency of -a 3.7 deletion has been reported to be rather high as in other populations of Mediterranean basin [4,5]. The most common genotypes in Iraq were -a 3.7 /aa, -MED /aa and -a 3.7 /-a 3.7 which were detected in 65.1 % of the study group [6]. In the present study, 12 different alleles and 29 genotypes were identified.…”

“…Alpha-thalassemia is an autosomal recessive disorder characterized by microcytic hypochromic anemia and a clinical phenotype varying from almost-asymptomatic to lethal hemolytic anemia [6]. Alpha-thalassemia is often initially suspected on the basis of a routine full blood count.…”

Understanding Beta-Thalassemia with Focus on the Indian Subcontinent and the Middle East

“…Molecular testing of 104 (50 male, 54 female) registered beta-thalassemia patients from Dohuk detected 12 mutations. The eight most common mutations observed accounted for 81.7% of the thalassemia alleles [51]. The mutations in descending order of frequency were: c.315+1G>A, c.135delC, c.17_18delCT, c.92+1G>A, c.92+6T>C, c.118C>T, c.27_28insG, and c.92+5G>C ( Table 2).…”

“…In Iraq, beta-thalassemia is an evident health problem, specifically in the Dohuk region located in the northern part of the country [51]. The Dohuk region lies midway between Iran, Turkey and Syria, countries also characterized by a relatively high frequency of beta-thalassemia.…”

“…The Dohuk region lies midway between Iran, Turkey and Syria, countries also characterized by a relatively high frequency of beta-thalassemia. The disease prevalence in Dohuk is reinforced by the high rate of consanguineous marriages in the region, which were estimated at 25.3% [51]. Molecular testing of 104 (50 male, 54 female) registered beta-thalassemia patients from Dohuk detected 12 mutations.…”