Molecular patterns of alpha-thalassemia in the kingdom of Saudi Arabia: identification of prevalent genotypes and regions with high incidence.

Background: Alpha-thalassemia (α-thalassemia) is one of the most common monogenic diseases in Saudi Arabia and is associated with significant morbidity. Premarital testing programs in Saudi Arabia reduce the burden of hemoglobinopathy disorders, and ongoing monitoring is required. We aimed to explore the molecular nature of α-globin genes and identify the most common genotypes and regions with a high risk of α-thalassemia in Saudi Arabia.

Methods: This retrospective study was conducted between January 2021 and December 2022. Six hundred twenty-five samples from patients with microcytic hypochromic anemia in Saudi Arabia were analyzed using reverse dot blot hybridization (RDBH)-based multiplex-PCR, which screens for the known 21 mutations of α-globin genes.

Results: Seven mutations in the α-globin gene were identified in 88.96% (556) patients. The most frequent abnormality of a-globin genes was -α^3.7 (62.3%), followed by α2^IVS1(-5nt) (20.7%) and α2 polyA-1 (α2^T.Saudi) (14.1%). Interestingly, α2 polyA-2 (α2^T.Turkish) was identified in Saudi and presented with -MED, causing Haemoglobin H disease. The incidence of α-thalassemia in Saudi Arabia's cities showed significant differences (P = 0.004). Jeddah City had the highest percentage of cases (25%), followed by Makkah (23%), Taif (13.3%), and Al-Ahassa (12.4%).

Conclusion: The study provides current knowledge about the molecular nature of α- thalassemia, highlights the common genotypes that could contribute to disease occurrence in the Saudi population, and sheds light on Saudi regions with a high incidence. It also recommends further studies in a larger population and with differently composed molecular assays to verify these findings.