Precise genetic analysis and reproductive guidance for two rare families with complex chromosomal rearrangements facilitated by optical genome mapping
10.3760/cma.j.cn511374-20250408-00212
- VernacularTitle:光学基因组图谱技术精准助力两个罕见复杂重排家系的遗传学分析及再生育指导
- Author:
Jiangyang XUE
1
;
Min XIE
1
;
Yuxin ZHANG
1
;
Yingwen LIU
1
;
Haibo LI
1
Author Information
1. 宁波大学附属妇女儿童医院出生缺陷综合防治中心 宁波市胚胎源性疾病防治重点实验室 宁波市基因组医学与出生缺陷防治重点实验室，宁波 315012
- Publication Type:Journal Article
- Keywords:
Optical genome mapping;
Rare complex chromosomal rearrangements;
Precise localization;
Reproductive guidance
- From:
Chinese Journal of Medical Genetics
2025;42(7):883-889
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.
