Diverse Genotype Presentation of the Saudi-Type Poly A Signal Mutation ( αTsaudiα ) in the Population of Bahrain

C l i n M e d International Library Citation: Al Moamen N, Mahdi F, Thabet A, Abbas R, Salman E, et al., (2015) Diverse Genotype Presentation of the Saudi-Type Poly A Signal Mutation (αTsaudiα) in the Population of Bahrain. Int J Blood Res Disord 1:004 Received: December 28, 2014: Accepted: January 05, 2015: Published: January 15, 2015 Copyright: © 2015 Al Moamen N. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Moamen et al. Int J Blood Res Disord 2015, 2:1 ISSN: 2469-5696

α-Thalassemia is quite prevalent in the population of Bahrain reaching a frequency of 24.3% based on neonates screening of Hb Bart's in cord blood hemolysates [1].In a preliminary report we found five different α-thalassemia determinants as the underlying molecular defects for α-thalassemia in our population [2].The first most common α-thal determinant uncovered in that report was the Saudi-type polyadenylation signal mutation that is found in α2globin gene (α TSaudi α) [AATAAA ◊ AATAAG; c. * 94A>G] [2,3,4].In this letter we presented the diverse genotype combinations of the (α TSaudi α) haplotype in our population and their relevant phenotypes.
A total of 1187 patients with α-thalassemia phenotype presentation have been recruited for this investigation.Preliminary diagnosis of α-thalassemia was based on low hematological indices (MCV and MCH) of the red blood cells and/or persistently low hemoglobin levels, along with low or normal levels of HbA2 and absence of iron deficiency [5,6].The molecular diagnosis of α-thalassemia was established by using a commercially available α-thalassemia strip assay (α-Globin StripAssay, ViennaLab Diagnostics GmbH) and direct nucleotide sequencing for further confirmation.
The spectrum of phenotype presentations for the (α TSaudi α) genotype combinations ranges between hemoglobin H (Hb H) disease and α-thalassemia trait phenotype with variable severity.
The first molecular defect causing HbH disease in our population is homozygosity for the (α TSaudi α) haplotype, i.e., the (α TSaudi α/α TSaudi α) genotype, which is by far the most common molecular basis of Hb H disease in this population.A total of 49 patients were uncovered with this genotype and a representative 15 patients are introduced in Table 1.These patients are presented with moderate to severe level of anemia (Hb ranges: 7.4-9.7g/dL).They persistently show Hb H peak fraction on HPLC of their RBC hemolysates with HbH level ranges from 7.5 to 27.2 % of total hemoglobin.In addition, most of these patients are presented with elevated level of reticulocytes (>3.0%), an indication of hematopoitic stress due to persistent anemia.Moreover, significant number of these patients is undergoing infrequent blood transfusion which is in line with variable phenotype presentation of Hb H disease in other populations [7][8][9].Although this genotype is inactivating only two α-globin genes it gives rise to a severe form of Hb H disease whereas the inactivation of three α-globin genes is commonly encountered in Hb H disease [10].This unusual effect of the (α TSaudi α) mutation is largely attributed to a down regulation effect of this mutation on the linked α1-globin gene as a result of transcriptional interference as was suggested before [11,12].
The second genotype underlying Hb H disease in this population is compound heterozygosity of the (α TSaudi α) haplotype in trans with the IVS I donor-site pentanucleotide deletion mutant in α2-globin gene on the other chromosome [(α Hph α/); c.95+2_95+6del TGAGG] [13].This genotype combination [i.e., (α TSaudi α/α Hph α)] was discovered in a total of 25 patients and all are presented with relatively mild-tomoderate form of Hb H disease with total Hb levels ranging from
In summary, this report presents our findings in regard of the (α TSaudi α) genotype combinations in the population of Bahrain and their phenotypes.Further investigations in various developmental stages are warranted to clearly understand the natural history of (α TSaudi α) genotype combinations.

Table 3 :
Average hematological values for patients harboring various combinations of the (α TSaudi α) genotype along with values for wild type genotype (αα/αα) in the population of Bahrain *Values are means (±SD)