Zhu Wenxiu, Wang Yankun, Wang Lei, Li Beiqing, Wei Han, Zhang Yang, He Guiyuan, Fei Jia, Shi Ming
Center for Reproductive and Genetic Medicine, Dalian Women and Children's Medical Group, Dalian, Liaoning 116037, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 Jul 10;42(7):862-868. doi: 10.3760/cma.j.cn511374-20250526-00330.
To block family transmission of a small fragment copy number variation (CNV) with combined 1 Mb resolution preimplantation genetic testing for aneuploidy (PGT-A) and target region preimplantation genetic testing for monogenic disease (PGT-M) strategies.
A couple who attended the Reproductive and Genetic Medicine Center of Dalian Women and Children's Medical Center (Group) in 2024 were selected as the study subject. Upon the woman's two pregnancies, ultrasound examination revealed fetal abnormalities, and CNV-seq based on low-depth whole genome sequencing revealed that both fetuses had carried a maternal 17p12 microduplication of approximately 1.43 Mb. Microduplication in this region has been associated with Charcot-Marie-Tooth disease type 1A. In view of the fact that the resolution of conventional PGT-A detection cannot meet the requirement of small fragment CNV analysis, and conventional PGT-M assay cannot directly determine the CNV, two detection schemes were adopted. On the one hand, PGT-A testing with 1 Mb resolution was performed on the embryo to directly determine whether it carries the above microduplication. At the same time, the couple and their fetus were subjected to chromosomal typing scheme for the 17p12 region to indirectly identify embryos carrying the risk chromosome for microduplication. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No: FEJT-KY-2025-51).
Three embryos were tested after the first PGT cycle, of which 1 was not carrying the pathogenic variant and was euploid, whilst the other 2 embryos were carrying the 17p12 microduplication, and 1 of them was aneuploid. After genetic counseling, the euploid embryo without the 17p12 microduplication was selected for transfer, and prenatal diagnosis based on amniotic fluid sample showed that the fetal chromosomal karyotype was normal and did not carry the 17p12 microduplication.
The combined application of high-resolution PGT-A and PGT-M typing detection of the target region can effectively block family transmission of the CNVs of small fragments.
采用1兆碱基分辨率的联合胚胎植入前非整倍体基因检测（PGT-A）和单基因疾病目标区域胚胎植入前基因检测（PGT-M）策略，阻断一个小片段拷贝数变异（CNV）的家族遗传。
选取2024年到大连妇女儿童医疗中心（集团）生殖与遗传医学中心就诊的一对夫妇作为研究对象。该女性两次怀孕时，超声检查均显示胎儿异常，基于低深度全基因组测序的CNV-seq检测显示，两个胎儿均携带母亲17p12区域约1.43兆碱基的微重复。该区域的微重复与1A型遗传性运动感觉神经病相关。鉴于传统PGT-A检测分辨率无法满足小片段CNV分析需求，且传统PGT-M检测无法直接判定CNV，故采用两种检测方案。一方面，对胚胎进行1兆碱基分辨率的PGT-A检测，直接判定其是否携带上述微重复。同时，对夫妇及其胎儿进行17p12区域的染色体分型检测，间接识别携带微重复风险染色体的胚胎。本研究已获医院医学伦理委员会批准（伦理编号：FEJT-KY-2025-51）。
首次PGT周期后检测了3个胚胎，其中1个未携带致病变异且为整倍体，另外2个胚胎携带17p12微重复，其中1个为非整倍体。经遗传咨询后，选择未携带17p12微重复的整倍体胚胎进行移植，羊水样本产前诊断显示胎儿染色体核型正常，未携带17p12微重复。
高分辨率PGT-A与目标区域PGT-M分型检测联合应用可有效阻断小片段CNV的家族遗传。
