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. 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. Seven mutations in the α-globin gene were identified in 88.96% (556) patients. The most frequent abnormality of a-globin genes was −α3.7 (62.3%), followed by α2IVS1(−5nt) (20.7%) and α2 polyA-1 (α2T.Saudi) (14.1%). Interestingly, α2 polyA-2 (α2T.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%). 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.

中文翻译：

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沙特阿拉伯王国α-地中海贫血的分子模式：流行基因型和高发地区的识别

α-地中海贫血（α-地中海贫血）是沙特阿拉伯最常见的单基因疾病之一，发病率很高。沙特阿拉伯的婚前检测项目减轻了血红蛋白病疾病的负担，并且需要持续监测。我们的目的是探索 α-珠蛋白基因的分子性质，并确定沙特阿拉伯最常见的基因型和 α-地中海贫血高风险区域。这项回顾性研究于 2021 年 1 月至 2022 年 12 月期间进行。使用基于反向点印迹杂交 (RDBH) 的多重 PCR 对来自沙特阿拉伯小细胞低色素性贫血患者的 625 个样本进行了分析，筛选了已知的 21 个突变α-珠蛋白基因。在 88.96% (556) 的患者中发现了 7 个 α-珠蛋白基因突变。a-珠蛋白基因最常见的异常是-α3.7 (62.3%)，其次是α2IVS1(-5nt) (20.7%) 和α2 polyA-1 (α2T.Saudi) (14.1%)。有趣的是，α2polyA-2（α2T.Turkish）在沙特被鉴定出来并呈-MED，导致血红蛋白 H 病。沙特阿拉伯各城市α-地中海贫血的发病率存在显着差异（P = 0.004）。吉达市的病例比例最高（25%），其次是麦加（23%）、塔伊夫（13.3%）和阿哈萨（12.4%）。该研究提供了有关α-地中海贫血分子性质的最新知识，强调了可能导致沙特人口中疾病发生的常见基因型，并揭示了沙特高发地区的情况。它还建议在更大的人群中进行进一步的研究，并使用不同组成的分子测定来验证这些发现。