Enhancing thalassemia carrier detection: Advancing genetic screening strategies in prenatal care

The carrier rates of alpha- and beta-thalassemia are notably high in certain regions. Current screening methods using traditional mean corpuscular volume (MCV) measurements can prevent the birth of severe cases of thalassemia, but often miss carriers of mild forms, potentially leading to hemoglobin H disease or thalassemia in their offspring. This study aimed to demonstrate that genetic carrier screening using next-generation sequencing (NGS) enhances the detection of silent thalassemia carriers and explores its clinical feasibility for large-scale population screening to illustrate the prevalence and spectrum of thalassemia in Taiwan. This retrospective study was conducted in Taiwan between April 1, 2019 and August 30, 2022. Of 1901 screened patients, 174 thalassemia carriers were identified, indicating a carrier rate of 9.2 %. The prevalence of alpha-thalassemia, beta-thalassemia, and combined alpha- and beta-thalassemia was 7.8 %, 1.3 %, and 0.1 %, respectively. Specifically, 84.5 %, 13.8 %, and 1.1 % of the patients had alpha-thalassemia, beta-thalassemia, and both types of thalassemia, respectively. These carrier rates were higher than those reported in previous studies. Among alpha-thalassemia carriers, the SEA (Southeast Asian) type was the most prevalent at 52.7 %, followed by the right-end deletion type (-α3.7) at 30.4 %. Using the MCV cut-off method would have missed 33.8 % and 12.5 % of alpha- and beta-thalassemia carriers, respectively. Screening for thalassemia carriers based solely on MCV leads to a high rate of misdiagnosis. To our knowledge, this study is the first to apply NGS to analyze the distribution of thalassemia in Taiwan, offering a valuable foundation for screening, prevention, and treatment strategies.