摘要目的:应用光学基因组图谱技术(OGM)对2个罕见复杂染色体重排家系进行分析，为其提供精准的再生育指导。方法:选取2023年6月至12月在宁波大学附属妇女儿童医院经染色体微阵列分析(CMA)或全外显子组测序(WES)检测确诊为染色体异常，可能存在染色体不平衡易位的2例胎儿家系为研究对象，收集相关的临床资料，采集怀孕夫妇的外周血样、胎儿羊水以及流产物样本，对其进行G显带核型分析联合OGM技术进行全面检测。本研究通过了本院医学伦理委员会的审查(批准号：EC2023-094)。结果:家系1孕妇因无创产前检测提示7号染色体异常接受羊水穿刺CMA检测；家系2孕妇孕10周发生胚胎停育，流产物送检家系WES。2个家系的胎儿均检出染色体拷贝数变异(CNVs)，疑似存在复杂染色体不平衡易位。经OGM技术验证，家系1的胎儿和母亲染色体均存在非平衡性结构重排，涉及7、8、10号染色体的复杂易位，形成der(8)和der(10)两条衍生染色体；家系2母亲的2号及13号染色体发生复杂重排，涉及7处染色体断裂点。经遗传咨询，家系1考虑胎儿的染色体复杂重排遗传自表型正常的母亲，决定继续妊娠。鉴于2个家系再生育仍面临染色体非平衡重排的风险，建议届时进行胚胎植入前遗传学检测。结论:OGM检测明确了2例胎儿CNVs的发生机制，精确定位了其母源染色体复杂易位的区带及断裂点，为2个家系的遗传咨询及生殖干预提供了依据。

abstractsObjective:To apply optical genome mapping (OGM) technique for the analysis of genetic etiology in two rare families with complex chromosomal rearrangements (CCRs) and to provide precise reproductive guidance to them.Methods:Two Chinese families diagnosed with chromosomal rearrangements by chromosomal microarray analysis (CMA) or whole-exome sequencing (WES) between June and December 2023 at the Affiliated Women and Children′s Hospital of Ningbo University were selected as the study subjects. In both cases, unbalanced chromosomal translocations were suspected. Clinical data were collected, and peripheral blood from the couple, amniotic fluid sample and aborted fetal tissue was subjected to combined G-banding karyotyping and OGM for comprehensive genetic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethic No.: EC2023-094).Results:In family 1, the fetus was signaled to have abnormal chromosome 7 by non-invasive prenatal testing (NIPT), prompting amniocentesis and CMA detection. In family 2, a pregnancy loss had occurred at 10 weeks′ gestation, and trio-WES was carried out. Both fetuses were found to harbor copy number variations (CNVs) suggestive of unbalanced CCRs. Further analysis with OGM has revealed that, in family 1, an unbalanced rearrangement involving chromosomes 7, 8, and 10 was carried by the fetus and the pregnant woman, which has formed der(8) and der(10) derivative chromosomes. In family 2, a maternal CCR was found, which involved chromosomes 2 and 13 with seven breakpoints, resulting in unbalanced fetal CNVs. After genetic counseling, family 1 opted to continue with the pregnancy, considering the woman′s normal appearance and inheritance of the rearrangement. For both families remained to have a risk for unbalanced rearrangements in subsequent pregnancies, preimplantation genetic testing (PGT) was recommended.Conclusion:In both families, the OGM has precisely delineated the genetic basis of fetal CNVs and mapped the maternal CCR breakpoints, providing critical insights for genetic counseling and reproductive decision-making.