Li H Y, Zhao Z H, Kong L R, Fu X Y, Zhu J Q, Wu S T, Sun L M, Kong X D
Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Department of Fetal Medicine & Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China.
Zhonghua Yi Xue Za Zhi. 2025 Feb 11;105(6):459-464. doi: 10.3760/cma.j.cn112137-20240614-01334.
To explore the value of noninvasive prenatal diagnosis for monogenic disorders (NIPD-M) based on relative haplotype dosage (RHDO) and Bayes factor (BF) for pregnant women with high-risk recessive genetic disease in the first trimester. A total of 206 pregnant women with high-risk recessive genetic disease and pedigree samples at the First Affiliated Hospital of Zhengzhou University between September 2022 and November 2023 were collected. The cell-free DNA (cfDNA) was extracted from the pregnant woman's plasma and the genomic DNA (gDNA) was extracted from the pedigree blood samples. The designed capture panel covered 10 genes (DMD, SMN1, PAH, MMACHC, MMUT, F8, F9, SLC26A4, GJB2, CYP21A2). Sequencing of target regions was performed through high-throughput sequencing platforms, informative single nucleotide polymorphism (SNP) was screened, and pathogenic haplotypes were constructed. The fetal genotype was determined based on the dose change of the informative SNPs in cfDNA combined with the BF algorithm. The circular binary segmentation (CBS) algorithm was used to exclude the interference of recombination events. All NIPD-M results were validated by invasive prenatal diagnosis or newborn genetic testing. Among the recruited families, the median (, ) age of the 206 pregnant women was 32 (27, 38) years, and the earliest blood collection was at 7 weeks of pregnancy, with the median (, ) blood collection time of 8 (8, 9) weeks and fetal fraction (FF) of 5.21% (3.56%, 7.64%). A total of 190 cases were successfully tested, while 16 failed the test, with a success rate of 92.2% (190/206). The NIPD-M results were consistent with the invasive prenatal diagnosis and newborn genetic testing, with the accuracy rate of 100% (190/190). NIPD-M provides an earlier and safer means of prenatal diagnosis for high-risk pregnant women with recessive genetic diseases, with high accuracy and rapid response.
探讨基于相对单倍型剂量（RHDO）和贝叶斯因子（BF）的无创产前诊断单基因疾病（NIPD-M）在孕早期高危隐性遗传病孕妇中的应用价值。收集了2022年9月至2023年11月期间郑州大学第一附属医院206例高危隐性遗传病孕妇及其家系样本。从孕妇血浆中提取游离DNA（cfDNA），从家系血样中提取基因组DNA（gDNA）。设计的捕获panel覆盖10个基因（DMD、SMN1、PAH、MMACHC、MMUT、F8、F9、SLC26A4、GJB2、CYP21A2）。通过高通量测序平台对目标区域进行测序，筛选信息性单核苷酸多态性（SNP），构建致病单倍型。结合BF算法，根据cfDNA中信息性SNP的剂量变化确定胎儿基因型。采用循环二元分割（CBS）算法排除重组事件的干扰。所有NIPD-M结果均通过侵入性产前诊断或新生儿基因检测进行验证。在所招募的家庭中，206例孕妇的年龄中位数（，）为32（27，38）岁，最早采血时间为妊娠7周，采血时间中位数（，）为8（8，9）周，胎儿游离DNA比例（FF）为5.21%（3.56%，7.64%）。共成功检测190例，16例检测失败，成功率为92.2%（190/206）。NIPD-M结果与侵入性产前诊断和新生儿基因检测结果一致，准确率为100%（190/190）。NIPD-M为高危隐性遗传病孕妇提供了一种更早、更安全的产前诊断方法，具有高准确性和快速反应性。
