Spectrum of α-Thalassemia Mutations in Transfusion-Dependent β-Thalassemia Patients from the Eastern Province of Saudi Arabia

Abstract

Both α- and β-thalassemia (α- and β-thal) are highly prevalent in the population of the Al-Qatif and Al-Ahsa regions in the Eastern Province of Saudi Arabia. This study provides a more precise picture of the α-thal mutations prevalent in 104 transfusion-dependent β-thal patients in the Eastern Province. Detection of α-thal mutations was carried out using the α-globin StripAssay kit. A total of 12 α-thal mutations (21 genotypes) were identified in 33.7% of the chromosomes (46 patients). The heterozygous and homozygous –α^3.7 (α⁺) deletion mutations were the most prevalent in the β-thal patients (21.7%). We identified three α⁰ deletions [– –^MED, – –^FIL and –(α)20.5] that have not been previously reported for the population of Saudi Arabia. The seven point mutations identified in the β-thal patients were: codon 14 [TGG>TAG (α1)], codon 59 [GGC>GAC (α1)] (Hb Adana), polyadenylation signal site (polyA1) [AATAAA>AATAAG (α2)], codon 142 [TAA>TCA (α2)] (Hb Koya Dora), codon 59 [GGC>GAC (α2)] (Hb Adana), initiation codon [ATG>ACG (α2)] and the ααα^{anti 3.7} gene triplication. The Hb Koya Dora mutation occurred at the highest frequency (15.38%). Comparison of the clinical phenotype of β-thal patients, with and without an α-thal mutation, showed that patients with β-thal alone had a significantly elevated level of alanine transaminase (ALT) (mean 72.5 IU/L) and aspartate transaminase (AST) (mean 71.8 IU/L) (p <0.005). In addition, the β-thal patients without an α-thal mutation had a higher percentage of osteoporosis (16.6%), fractures (12.5%), and splenectomies (58.3%). This confirms previous data that the co-inheritance of α-thal in β-thal patients results in the amelioration of the clinical phenotype of β-thal patients. Moreover, the high frequency of α- and β-thal in the Eastern Province of Saudi Arabia and their coinheritance, necessitates the inclusion of α-thal testing in the current pre marital testing program to highlight the risk to the offspring of affected individuals.

• Mutation
• α-Thalassemia (α-thal)
• β-Thalassemia (β-thal)
• Polymorphism
• Saudi Arabia

ACKNOWLEDGMENTS

We would like to extend our gratitude for the laboratory and technical expertise of Mr. Ranie Tumbaga (Prince Mohammed Centre for Research & Consultation Studies, University of Dammam, Saudi Arabia), Mr. Abdulrazag Al-Wabary, Mr. Ibrahim Al-Sager, and Mr. Hani Al-Farhan (Al-Omran Scientific Chair for Hematological Diseases in Al-Ahsa, King Faisal University, Al-Ahsa, Saudi Arabia).

Declaration of Interest

The authors would like to thank the University of Dammam, Deanship of Scientific Research and the Al-Omran Scientific Chair for Hematological Diseases at Al-Ahsa for the funding of this project. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.