Spectrum of β-Thalassemia Mutations in the Eastern Province of Saudi Arabia

Abstract

β-Thalassemias comprise a group of heterogeneous hemoglobin (Hb) disorders characterized by the absence or reduced synthesis of the β-globin chain with a variable clinical presentation. The Al-Qatif and Al-Ahsa oases in the Eastern Province of Saudi Arabia are regions known for the high prevalence of these disorders. This study was conducted to provide a more precise picture of the β-thalassemia (β-thal) mutations prevalent in these regions and to estimate their frequencies. One hundred and 96 subjects with transfusion-dependent β-thalassemia (β-thal) disease were included in this study. A total of 14 β-thal mutations were identified with five mutations accounting for more than 80% of the total β-thal mutations identified. Of the 196 patients, 164 were homozygous for a β-thal mutation, while 32 were compound heterozygotes. We report here the novel identification of two mutations, namely, the Tunisian splice site IVS-I-130 (G→C) and the Mediterranean cryptic splice site IVS-I-110 (G→A), which have not been previously reported in the population of the Eastern Province. However, 15 patients (46.9%) with compound heterozygosities carried one of the β-thal mutations and the sickle cell mutation [Hb S or β6(A3)Glu→Val]. These patients were less frequently transfused than the patients who were homozygous for the β-thal mutations and presented with fewer complications. A more comprehensive overview of the genetic heterogeneity of the β-thal mutations in the Eastern Province of Saudi Arabia is presented in this article. This study will contribute to the establishment of an effective prevention program, including premarital screening.

Co-inheritance of novel ATRX gene mutation and globin (α & β) gene mutations in transfusion dependent beta-thalassemia patients

“…Sickle cell disease, α-thalassemia and β-thalassemia are the most common monogenic disorders in the oasis of Qatif and Al-Ahsa in the Eastern Province of Saudi Arabia [5][6][7]17,18]. In our previous study of the prevalence of these disorders in the Eastern Province of Saudi Arabia, we confirmed the widespread coinheritance of α-thalassemia mutation in transfusion dependent β-thalassemia patients [6,7].…”

“…The study was approved by the University of Dammam Institutional Review Board and written informed consent was obtained from all participating subjects. All mutations in the transfusion dependent β-thalassemia patients had previously been identified and these patients were requested to donate an additional blood sample for the purpose of this study [5][6][7]. Accordingly, blood samples (5 mL) from all participating subjects were collected in EDTA vacutainers and analyzed using the α-globin StripAssays (cat for α 4-160, Vienna Lab Diagnostics GmbH, Vienna, Austria) to identify the α-thalassemia mutations.…”

“…Some of these subjects have a family history of mental retardation, the cause of which is unknown. β-thalassemia is caused by reduced or absent synthesis of the β-globin chains coded by two β-globin genes, one on each of chromosome 11 and α-thalassemia is caused by decreased or absent synthesis of the α-globin chains coded by four α genes, two on each chromosome 16 [5][6][7]. Although some of the patients with transfusion dependent β-thalassemia have a family history of mental retardation, to our knowledge, a study of ATRX gene mutations in β-thalassemia has not been previously conducted on this population [8].…”

Regional consensus opinion for the management of Beta thalassemia major in the Arabian Gulf area

“…β-Thalassemia is a group of heterogeneous autosomal recessive disorders arising due to the absence or reduced synthesis of the β-globin chain [18]. β-Thalassemia could be associated with severe congenital disorders caused by mutations in the β - globin gene resulting in the absence or reduced synthesis of the β-globin chain [1,12].…”

Mutations in the β‐globin gene from a Saudi population: an update

“…Sir, b-thalassemia is highly prevalent in the Al-Ahssa and Al-Qatif regions of the Eastern Province of Saudi Arabia [1][2][3][4][5] with extremely diverse clinical manifestations reflecting the heterogeneity of mutations at the b-globin locus. Approximately 200 mutations that lead to b-thalassemia have been identified in various populations, with each population characterized by specific common and rare mutations [6].…”