一个t(8;13)染色体平衡易位的家系遗传学分析

doi:10.12280/gjszjk.20250387

摘要/Abstract

摘要：

报告1个由染色体平衡易位导致多次不良孕产史家系的遗传学分析结果。收集家系成员的临床资料，采集家系成员外周血，行染色体核型分析、单核苷酸多态性微阵列（single nucleotide polymorphism array，SNP array）检测。先证者（女）表现为语言发育迟缓、智力低下、癫痫等，先证者的弟弟与先证者具有相似的表型。母亲孕8⁺²周时进行遗传咨询。染色体核型分析示父亲为t(8;13)(p23;q22)平衡易位携带者，SNP array检测结果提示16p13.11p12.3微缺失；母亲染色体核型及SNP array未见异常；先证者及其弟弟核型分析与父亲一致，SNP array检测结果均存在8p23.3区段缺失及13q31.1q34区段重复，同时先证者还遗传了父亲的16p13.11p12.3微缺失。母亲此次孕12⁺²周时超声提示胎儿颈后透明层厚度（nuchal translucency，NT）增厚等多发异常，孕14周胚胎停育，未行遗传学检查。8p23.3的缺失和13q31.1q34的重复为先证者及其弟弟异常表型的原因，先证者母亲既往两次自然流产及本次胚胎停育胎儿虽未检测，但也可能与此相关。故染色体平衡易位携带者夫妇妊娠需进行遗传学咨询及产前诊断。

关键词: 易位，遗传, 多态性，单核苷酸, 核型分析, 微阵列分析, 妊娠结局

Abstract:

We report a family with a history of multiple adverse reproductive outcomes due to a balanced chromosomal translocation. The clinical data and blood samples of the family's members were collected. Chromosomal karyotype and single nucleotide polymorphism array (SNP array) analysis were performed. The proband (female) presented with language developmental delay, intellectual disability, epilepsy and other manifestations, while her younger brother displayed a similar phenotype. The mother sought genetic counseling at 8⁺² weeks of gestation. Karyotype analysis revealed that the father was a carrier of a balanced translocation, t(8;13)(p23;q22), and SNP array testing showed a microdeletion in 16p13.11p12.3. The karyotype and SNP array results of mother were normal. Both the proband and her brother had the karyotype being consistent with the father's translocation, and the SNP array results being an 8p23.3 deletion and a 13q31.1q34 duplication. Additionally,the proband inherited the father's 16p13.11p12.3 microdeletion. At 12⁺² weeks of the current pregnancy, the ultrasound revealed multiple abnormalities in the fetus, including increased nuchal translucency (NT) thickness. The pregnancy ended in embryonic demise at 14 weeks, and no genetic testing was performed. The 8p23.3 deletion and 13q31.1q34 duplication were responsible for the abnormal phenotypes in the proband and her brother. Although not tested, the two spontaneous miscarriages and this embryonic arrest may share the same underlying cause. Therefore, the couples where one partner is a balanced translocation carrier require genetic counseling and prenatal diagnosis.

Key words: Translocation, genetic, Polymorphism, single nucleotide, Karyotyping, Microarray analysis, Pregnancy outcome

蔡丽怡, 江矞颖, 庄倩梅, 陈新英. 一个t(8;13)染色体平衡易位的家系遗传学分析[J]. 国际生殖健康/计划生育杂志, 2026, 45(1): 18-22.

CAI Li-yi, JIANG Yu-ying, ZHUANG Qian-mei, CHEN Xin-ying. The Genetic Etiology Analysis of A t(8;13) Balanced Chromosomal Translocation Family[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(1): 18-22.

图/表 5

图1 患者家系图注：箭头所示为先证者。

图2 家系染色体核型分析结果注：A 先证者；B 先证者弟弟；C 先证者母亲；D 先证者父亲；箭头所示为异常核型。

图3 先证者SNP array分析结果注：A 染色体模拟核型图；B 8号染色体部分缺失；C 13号染色体部分重复；D 16号染色体部分缺失。

图4 先证者弟弟SNP array分析结果注：A 染色体模拟核型图；B 8号染色体部分缺失；C 13号染色体部分重复。

图5 先证者父亲SNP array分析结果注：A 染色体模拟核型图；B 16号染色体部分缺失。

参考文献 15

[1]	黄婷婷, 张剑, 陈小露, 等. 88例平衡易位携带者孕中期产前诊断结果分析[J]. 中国妇幼保健, 2021, 36(21):5061-5063. doi: 10.19829/j.zgfybj.issn.1001-4411.2021.21.054.
[2]	ISCN 2024-An International System for Human Cytogenomic Nomenclature (2024)[J]. Cytogenet Genome Res, 2024, 164(Suppl 1):1-224. doi: 10.1159/000538512.
[3]	Kearney HM, Thorland EC, Brown KK, et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants[J]. Genet Med, 2011, 13(7):680-685. doi: 10.1097/GIM.0b013e3182217a3a. pmid: 21681106
[4]	Chen CP, Chern SR, Hsu CY, et al. Prenatal diagnosis of de novo partial trisomy 13q (13q22 --> qter) and partial monosomy 8p (8p23.3 --> pter) associated with holoprosencephaly, premaxillary agenesis, hexadactyly, and a hypoplastic left heart[J]. Prenat Diagn, 2005, 25(4):334-336. doi: 10.1002/pd.1126.
[5]	Abuhamda A, Elsous A, Sharif FA. Partial Trisomy of Chromosome 13 with a Novel Translocation (8;13) and Unique Clinical Presentation in a Palestinian Infant[J]. Case Rep Med, 2019, 2019:4561761. doi: 10.1155/2019/4561761.
[6]	Gilgenkrantz S, Defeche C, Stehlin S, et al. Proximal trisomy 13. A family with balanced reciprocal translocation t(8;13) in seven members and Robertsonian translocation t(13;14) in three members[J]. Hum Genet, 1981, 58(4):436-440. doi: 10.1007/BF00282833. pmid: 7327568
[7]	Atack E, Fairtlough H, Smith K, et al. A novel (paternally inherited) duplication 13q31.3q32.3 in a 12-year-old patient with facial dysmorphism and developmental delay[J]. Mol Syndromol, 2014, 5(5):245-250. doi: 10.1159/000358538. pmid: 25337073
[8]	Catusi I, Garzo M, Capra AP, et al. 8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature[J]. Genes (Basel), 2021, 12(5):652. doi: 10.3390/genes12050652.
[9]	Allen NM, O'hIci B, Anderson G, et al. Variant late-infantile neuronal ceroid lipofuscinosis due to a novel heterozygous CLN8 mutation and de novo 8p23.3 deletion[J]. Clin Genet, 2012, 81(6):602-604. doi: 10.1111/j.1399-0004.2011.01777.x.
[10]	Vantaggiato C, Redaelli F, Falcone S, et al. A novel CLN8 mutation in late-infantile-onset neuronal ceroid lipofuscinosis (LINCL) reveals aspects of CLN8 neurobiological function[J]. Hum Mutat, 2009, 30(7):1104-1116. doi: 10.1002/humu.21012. pmid: 19431184
[11]	陈新英, 潘汉斌, 曾书红, 等. 罕见的8p部分缺失伴重复患儿1例的临床及遗传学分析[J]. 中华医学遗传学杂志, 2023, 40(1):96-100. doi: 10.3760/cma.j.cn511374-20220112-00029.
[12]	Ranta S, Zhang Y, Ross B, et al. The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8[J]. Nat Genet, 1999, 23(2):233-236. doi: 10.1038/13868. pmid: 10508524
[13]	Rosenfeld JA, Coe BP, Eichler EE, et al. Estimates of penetrance for recurrent pathogenic copy-number variations[J]. Genet Med, 2013, 15(6):478-481. doi: 10.1038/gim.2012.164. pmid: 23258348
[14]	Goh S, Thiyagarajan L, Dudding-Byth T, et al. A systematic review and pooled analysis of penetrance estimates of copy-number variants associated with neurodevelopment[J]. Genet Med, 2025, 27(1):101227. doi: 10.1016/j.gim.2024.101227.
[15]	《胚胎植入前遗传学诊断/筛查专家共识》编写组. 胚胎植入前遗传学诊断/筛查技术专家共识[J]. 中华医学遗传学杂志, 2018, 35(2):151-155. doi: 10.3760/cma.j.issn.1003-9406.2018.02.001.