Prevalence and clinical significance of α-globin gene subtypes in prenatal thalassemia screening: a focus on the -α3.7III variant in Sanya, Hainan, China

Introduction Alpha-thalassemia is a common genetic disorder in southern China. The - α 3.7 deletion has three subtypes (I, II, III), among which type III has been rarely reported in the Chinese population. This study aimed to investigate the prevalence, genotypic distribution, and hematological phenotypes of the - α 3.7III subtype in Sanya, Hainan. Methods A total of 474 reproductive-age individuals undergoing prenatal thalassemia screening were enrolled from February 2022 to April 2025. Peripheral blood samples were collected, and genetic testing was performed using next-generation sequencing, with multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing as supplements. Results Among 474 subjects, 182 (38.40%) carried thalassemia mutations, including 149 (31.43%) with α -thalassemia. The most common α -thalassemia genotype was α α/- α 3.7I (9.70%), followed by α α/α Hb Westmead α (6.12%). A total of 38 - α 3.7III carriers with a detection rate of 8.02% (38/474), 89.50% of whom were of the Hui ethnic group. Hematological analysis showed that - α 3.7III carriers exhibited typical microcytic hypochromic features, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels were significantly lower in all - α 3.7 -related genotypes than in controls (all P < 0.001), while hemoglobin (Hb) levels showed no significant difference ( P = 0.779). Hematological phenotypes were comparable between - α 3.7I and - α 3.7III heterozygotes. Discussion This study is the first to report a high prevalence of the - α 3.7III subtype in the Hainan Hui population, enriching the genetic epidemiological data of α-thalassemia in China. Given that this variant may escape detection by conventional gap-PCR, undiagnosed - α 3.7III carriers are at substantial risk of transmitting this mutation to their offspring; when inherited in combination with other α 0 -thalassemia determinants, including --SEA, --FIL, --THAI, and other related genotypes, there is a significant risk of transfusion-dependent Hb H disease in offspring. These findings support the clinical necessity of comprehensive subtype screening and targeted testing in prenatal diagnosis.