Chen Yao, Liu Danyong, Yang Fang, Xiong Li, Shang Xuan, Liu Siping, Li Meng, Zhong Mei
Department of Obstetrics, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong Province, China.
Department of Obstetrics and Gynecology, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Medicine (Baltimore). 2025 Aug 22;104(34):e44014. doi: 10.1097/MD.0000000000044014.
This study evaluated the clinical utility of a target capture sequencing technique with a "pseudotetraploid" model for noninvasive prenatal testing of β-thalassemia in high-risk pregnancies. A prospective case series included 24 pregnant women with confirmed β-thalassemia carrier status. Cell-free DNA from maternal plasma was analyzed using a custom panel targeting common β-thalassemia mutations. Fetal genotypes were estimated using the "pseudotetraploid" model, and results were compared with invasive diagnostic findings. All 24 samples met DNA quality criteria, with 19 confirmed fetal thalassemia cases (13 β-thalassemia, 5 carriers, 1 unaffected). The detection rate was 79.17%, with a sensitivity of 89.47% (95% confidence interval [CI]: 77.56%-95.67%), specificity of 90.00% (95% CI: 69.77%-97.94%), positive predictive value of 97.14% (95% CI: 84.28%-99.94%), and negative predictive value of 69.23% (95% CI: 42.06%-88.43%). No fetal aneuploidies were detected. The findings support the clinical applicability of this noninvasive prenatal testing method for β-thalassemia, demonstrating high diagnostic accuracy and potential for multiplex genetic screening in a single assay, improving prenatal care efficiency.
本研究评估了一种采用“假四倍体”模型的靶向捕获测序技术在高危妊娠β地中海贫血无创产前检测中的临床应用价值。一项前瞻性病例系列研究纳入了24例确诊为β地中海贫血携带者状态的孕妇。使用针对常见β地中海贫血突变的定制检测板分析母血血浆中的游离DNA。采用“假四倍体”模型估算胎儿基因型，并将结果与侵入性诊断结果进行比较。所有24个样本均符合DNA质量标准，其中19例确诊为胎儿地中海贫血病例（13例β地中海贫血、5例携带者、1例未受影响）。检测率为79.17%，灵敏度为89.47%（95%置信区间[CI]：77.56%-95.67%），特异性为90.00%（95%CI：69.77%-97.94%），阳性预测值为97.14%（95%CI：84.28%-99.94%），阴性预测值为69.23%（95%CI：42.06%-88.43%）。未检测到胎儿非整倍体。这些发现支持了这种β地中海贫血无创产前检测方法的临床适用性，证明了其具有较高的诊断准确性以及在单一检测中进行多重基因筛查的潜力，可提高产前护理效率。
