Zhao Ganye, Liu Lina, Shi Panlai, Gu Mingxin, Yang Shaozhe, Kong Xiangdong
Department of Obstetrics and Gynecology, The Genetics and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Reproductive Medicine and Genetics, Pingdingshan Maternal and Child Health Hospital, Pingdingshan, China.
Am J Perinatol. 2025 Jul;42(9):1135-1140. doi: 10.1055/a-2459-8924. Epub 2024 Nov 4.
This study aims to assess the feasibility of detecting and diagnosing Duchenne muscular dystrophy (DMD) during prenatal screening for chromosome abnormalities using cell-free fetal DNA extracted from peripheral blood samples of pregnant women.Two pregnant women identified as high risk through noninvasive prenatal testing (NIPT) underwent amniocentesis to obtain fetal cells. Subsequent fetal chromosomal karyotyping was conducted, and genomic DNA from fetal cells was extracted for copy number variation sequencing (CNV-Seq) analysis, complemented by multiplex ligation-dependent probe amplification (MLPA) to detect deletions or duplications within the DMD gene.NIPT results for the two samples indicated potential abnormalities involving chromosomes 21 and 18. However, karyotype analysis of the fetuses revealed no abnormalities. CNV-Seq identified deletions of 0.28 and 0.18 Mb within chromosome Xp21.1, encompassing the DMD gene, in each fetus. In family 1, MLPA results indicated a maternal heterozygous deletion spanning exons 12 to 41 in the DMD gene, while the fetus exhibited deletions in exons 12 to 41. In family 2, MLPA results confirmed normal DMD gene status in the pregnant woman's peripheral blood genomic DNA but revealed a fetal deletion spanning exons 48 to 52. Both fetuses were diagnosed with DMD and subsequently underwent termination.Abnormalities identified through NIPT necessitate further invasive prenatal diagnostic procedures. For cases involving chromosomal microdeletions or microduplications, a combination of karyotyping and CNV-Seq testing is essential for comprehensive diagnosis. NIPT followed by CNV-Seq may offer insights into large exon deletions within the DMD gene in specific instances. · NIPT results can offer valuable insights into the deletion and duplication of DMD gene for the fetus.. · It's crucial to notice unexpected findings in NIPT.. · A combination of karyotyping and CNV-Seq testing is essential for comprehensive diagnosis..
本研究旨在评估利用从孕妇外周血样本中提取的游离胎儿DNA在染色体异常产前筛查期间检测和诊断杜氏肌营养不良症（DMD）的可行性。两名通过无创产前检测（NIPT）被确定为高风险的孕妇接受了羊膜穿刺术以获取胎儿细胞。随后进行了胎儿染色体核型分析，并提取胎儿细胞的基因组DNA进行拷贝数变异测序（CNV-Seq）分析，同时辅以多重连接依赖探针扩增（MLPA）以检测DMD基因内的缺失或重复。两个样本的NIPT结果表明存在涉及21号和18号染色体的潜在异常。然而，胎儿的核型分析未发现异常。CNV-Seq在每个胎儿的Xp21.1染色体上鉴定出0.28和0.18 Mb的缺失，该区域包含DMD基因。在家族1中，MLPA结果表明母亲在DMD基因中存在外显子12至41的杂合缺失，而胎儿在外显子12至41中也存在缺失。在家族2中，MLPA结果证实孕妇外周血基因组DNA中DMD基因状态正常，但显示胎儿存在外显子48至52的缺失。两个胎儿均被诊断为DMD，随后终止妊娠。通过NIPT识别出的异常需要进一步的侵入性产前诊断程序。对于涉及染色体微缺失或微重复的病例，核型分析和CNV-Seq检测相结合对于全面诊断至关重要。在特定情况下，NIPT后进行CNV-Seq可能有助于了解DMD基因内的大片段外显子缺失。· NIPT结果可为胎儿DMD基因的缺失和重复提供有价值的见解。· 注意NIPT中的意外发现至关重要。· 核型分析和CNV-Seq检测相结合对于全面诊断至关重要。
