光学基因组图谱技术在隐匿性复杂染色体平衡易位家系中的遗传学诊断应用

刘雅儒; 范睿; 吉亭亭; 许晓娟; 惠玲; 马晓玲

doi:10.11817/j.issn.1672-7347.2026.250555

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短篇论著 | 更新时间：2026-05-05

光学基因组图谱技术在隐匿性复杂染色体平衡易位家系中的遗传学诊断应用
Application of optical genome mapping technology in the genetic diagnosis of a family with a cryptic complex chromosomal balanced translocations
中南大学学报(医学版) 中南大学学报(医学版) 2026年51卷第2期页码：341-349
作者机构：

1.兰州大学第一临床医学院，兰州 730000
2.兰州大学第一医院生殖医学中心，兰州 730000
3.甘肃省生殖疾病临床医学研究中心，兰州 730000
4.甘肃省妇幼保健院(甘肃省中心医院)医学遗传中心，兰州 730000
作者简介：

刘雅儒，Email: 19996195063@163.com, ORCID: 0009-0005-6749-7474
马晓玲，教授，Email: maxl2005@163.com, ORCID: 0000-0002-0724-9293
基金信息：

甘肃省创新基地和人才计划(21JR7RA391);甘肃省教育厅高校教师创新基金(2026B-013);兰州市科技计划项目(2025-2-26);兰州大学第一医院院内基金(ldyyyn2025-171┫。This work was supported by the Gansu Provincial Science and Technology Program ┣21JR7RA391);the First Hospital of Lanzhou University(ldyyyn2025-171)
DOI：10.11817/j.issn.1672-7347.2026.250555
中图分类号：
CSTR：
收稿：2025-09-30，

纸质出版：2026-02-28
稿件说明：

刘雅儒, 范睿, 吉亭亭, 许晓娟, 惠玲, 马晓玲. 光学基因组图谱技术在隐匿性复杂染色体平衡易位家系中的遗传学诊断应用[J]. 中南大学学报(医学版), 2026, 51(2): 341-349.

LIU Yaru, FAN Rui, JI Tingting, XU Xiaojuan, HUI Ling, MA Xiaoling. Application of optical genome mapping technology in the genetic diagnosis of a family with a cryptic complex chromosomal balanced translocations[J]. Journal of Central South University. Medical Science, 2026, 51(2): 341-349.
刘雅儒, 范睿, 吉亭亭, 许晓娟, 惠玲, 马晓玲. 光学基因组图谱技术在隐匿性复杂染色体平衡易位家系中的遗传学诊断应用[J]. 中南大学学报(医学版), 2026, 51(2): 341-349. DOI：10.11817/j.issn.1672-7347.2026.250555.

LIU Yaru, FAN Rui, JI Tingting, XU Xiaojuan, HUI Ling, MA Xiaoling. Application of optical genome mapping technology in the genetic diagnosis of a family with a cryptic complex chromosomal balanced translocations[J]. Journal of Central South University. Medical Science, 2026, 51(2): 341-349. DOI：10.11817/j.issn.1672-7347.2026.250555.

摘要

目的

对于有反复不良孕产史但常规核型分析未见异常者，其潜在的遗传学病因(如隐匿性染色体平衡易位)难以通过传统方法明确。这类复杂结构变异因分辨率限制常被漏诊，成为临床遗传学诊断的难点之一。本研究对有2次异常生育史的夫妇进行遗传学病因诊断及生育指导，旨在为光学基因组图谱(optical genome mapping，OGM)技术在生殖遗传领域的拓展应用提供依据。

方法

收集于兰州大学第一医院生殖医学中心就诊、连续2次不良妊娠结局、寻求遗传学病因诊断的1对夫妇的临床资料，包括既往超声检查、染色体核型检查、拷贝数变异测序(copy number variation sequencing，CNV-seq)、荧光原位杂交(fluorescence in situ hybridization，FISH)技术结果。进一步采用OGM技术对夫妇双方外周血样本进行高分辨率全基因组结构变异分析，评估OGM在隐匿性染色体平衡易位，尤其是复杂结构变异诊断中的临床应用价值。

结果

该夫妇2次妊娠胎儿的CNV-seq结果分别显示为del(4)(p16.3)，3.80 Mb及dup(4)(p16.3)，3.74 Mb合并del(22)(q13.31~q13.33)，4.64 Mb。夫妻双方外周血染色体核型分析均未见明显异常，提示可能为隐匿性染色体平衡易位携带者。OGM检测结果显示，男方携带涉及1、4、22号染色体的隐匿性复杂平衡易位，其断裂点位于与2次胎儿CNV-seq异常片段边界一致的区域内，证实男方为表型正常的复杂平衡易位携带者，2次胎儿的染色体异常均为其亲代减数分裂过程中衍生染色体不平衡分离所致。

结论

OGM作为一种高分辨率、超长读长、自动化的新型非测序基因检测技术，在隐匿性平衡易位的检测方面相较于传统细胞遗传学技术更高效。

Abstract

Objective

For couples with recurrent adverse pregnancy outcomes but normal results on conventional karyotype analysis

the underlying genetic causes (such as cryptic chromosomal balanced translocations) are difficult to identify using traditional methods. These complex structure variations are often missed due to resolution limitations

posing a major challenge in clinical genetic diagnosis. This study aims to perform genetic etiological diagnosis and provide reproductive guidance for a couple with two abnormal reproductive histories

and to evaluate the application value of optical genome mapping (OGM) in the field of reproductive genetics.

Methods

Clinical data were collected from a couple who attended the Reproductive Medicine Center

First Hospital of Lanzhou University

with two consecutive adverse pregnancy outcomes and seeking genetic diagnosis. Previous results from ultrasonography

chromosomal karyotyping

copy number variation sequencing (CNV-seq)

and fluorescence in situ hybridization (FISH) were reviewed. OGM was further performed on peripheral blood samples from both partners to conduct high-resolution

genome-wide structural variation analysis

in order to assess the clinical utility of OGM in detecting cryptic chromosomal balanced translocations

particularly complex structure variations.

Results

CNV-seq results from the 2 pregnancies showed del(4)(p16.3)

3.80 Mb

and dup(4)(p16.3)

3.74 Mb combined with del(22)(q13.31-q13.33)

4.64 Mb

respectively. Conventional chromosomal karyotyping of peripheral blood from both parents revealed no obvious abnormalities

suggesting the possibility of a cryptic chromosomal balanced translocation carrier. OGM analysis demonstrated that the male partner carried a cryptic complex balanced translocation involving chromosomes 1

and 22. The breakpoints were located in regions consistent with the boundaries of the abnormal CNV segments identified in both fetuses. These findings confirmed that the male partner was a phenotypically normal carrier of a complex balanced translocation

and that the chromosomal abnormalities in both fetuses resulted from unbalanced segregation of derivative chromosomes during parental meiosis.

Conclusion

As a novel non-sequencing-based genomic technology characterized by high resolution

ultra-long read length

and automation

OGM is more efficient than traditional cytogenetic techniques in detecting cryptic balanced translocations.

关键词

Keywords

references

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