5个隐匿性平衡易位致不良妊娠结局家系的遗传学分析  

Cryptic balanced translocations leading to adverse pregnancy outcomes:genetic analysis of five pedigrees

作　　者：郭彩琴[1] 肖建平[1] 杨岚[1] 王峻峰[1] 崔玉[1] 桑泽玲 刘俊[2] Guo Caiqin;Xiao Jianping;Yang Lan;Wang Junfeng;Cui Yu;Sang Zeling;Liu Jun(Department of Medical Genetics and Prenatal Diagnosis,Wuxi Maternity and Child Health Care Hospital(Obstetrics and Gynecology Hospital Affiliated to Jiangnan University),Wuxi214002,China;Department of Ultrasonography,Wuxi Maternity and Child Health Care Hospital(Obstetrics and Gynecology Hospital Affiliated to Jiangnan University),Wuxi214002,China)

机构地区：[1]无锡市妇幼保健院(江南大学附属妇产医院)医学遗传与产前诊断科,无锡214002 [2]无锡市妇幼保健院(江南大学附属妇产医院)超声科,无锡214002

出　　处：《中华围产医学杂志》2024年第11期937-942,共6页Chinese Journal of Perinatal Medicine

基　　金：江苏省妇幼保健科研项目(F202205);无锡市医学创新团队项目(围产医学)(CXTD2021016);无锡市“双百”中青年医疗卫生拔尖人才项目(HB2023082)。

摘　　要：目的明确5个不良妊娠结局家系的遗传学病因,为指导遗传咨询及再生育提供参考。方法在2016年1月至2023年6月期间于无锡市妇幼保健院医学遗传与产前诊断科接受介入性产前诊断的孕妇中,共5例具有不良妊娠史且夫妻一方检出隐匿性平衡易位的孕妇,对其家系进行回顾性分析。常规G显带核型及染色体微阵列分析(chromosome microarray analysis,CMA)检测患儿/胎儿样本,并用染色体G显带和荧光原位杂交(fluorescence in situ hybridization,FISH)技术溯源,进而遗传咨询并随访妊娠结局。对数据采用描述性统计分析。结果例1长子不明原因智力障碍,CMA结果显示4p16.3p16.1区域8.6 Mb缺失及7q36.3区域1.0 Mb重复。例2~5本次妊娠胎儿均存在不平衡易位,分别为14q32.2q32.33区域6.1 Mb重复伴21q22.3区域1.6 Mb缺失(例2)、6q25.3q27区域10.8 Mb重复伴15q26.3区域1.2 Mb缺失(例3)、5p15.33区域1.0 Mb重复伴6q27区域2.9 Mb缺失(例4)和1q44区域3.2 Mb缺失伴19p13.3区域4.8 Mb重复(例5)。FISH验证后明确5个家系夫妻均有一方为隐匿性平衡易位的携带者。再对例3~4保留的前胎引产羊水行CMA检测,均提示存在不平衡易位。例1本次妊娠和例2遗传咨询指导后再妊娠产前诊断均未见异常,且均已生育健康后代,例3~5备孕中。结论遗传学技术联合应用明确了5个有不良妊娠史家系的遗传学病因为隐匿性平衡易位,为其再次妊娠的遗传咨询和干预提供了依据。ObjectiveTo identify the genetic causes of adverse pregnancy outcomes in five families and provide a basis for rational guidance on genetic and reproductive counseling.MethodsA retrospective analysis was conducted on five families with a history of adverse pregnancy outcomes,where one partner was found to have a cryptic balanced translocation.These cases were identified among pregnant women who underwent invasive prenatal diagnosis at the Department of Medical Genetics and Prenatal Diagnosis,Wuxi Maternity and Child Health Care Hospital,from January 2016 to June 2023.Conventional G-banding karyotyping and chromosomal microarray analysis(CMA)were performed on affected children/fetus samples.Chromosome G-banding and fluorescence in situ hybridization(FISH)were used for parental tracing.Genetic counseling was provided for all cases,and the pregnancy outcomes were followed up.Descriptive analysis was applied in this study.ResultsCase 1 involved an eldest son with unexplained intellectual disability,and the CMA results showed an 8.6 Mb deletion in the 4p16.3p16.1 region and a 1.0 Mb duplication in the 7q36.3 region.Unbalanced translocations were detected in the current pregnancies of the other four cases,which were a 6.1 Mb duplication in the 14q32.2q32.33 region with a 1.6 Mb deletion in the 21q22.3 region(Case 2),a 10.8 Mb duplication in the 6q25.3q27 region with a 1.2 Mb deletion in the 15q26.3 region(Case 3),a 1.0 Mb duplication in the 5p15.33 region with a 2.9 Mb deletion in the 6q27 region(Case 4),and a 3.2 Mb deletion in the 1q44 region with a 4.8 Mb duplication in the 19p13.3 region(Case 5).FISH confirmed that either the husband or the wife in each of the five families was a carrier of a cryptic balanced translocation.Further CMA testing on amniotic fluid samples from previous terminated pregnancies of Cases 3 and 4 also indicated unbalanced translocations.Both the current pregnancy of Case 1 and the subsequent pregnancy of Case 2 gave birth to healthy babies after non-abnormal prenatal diagnosis and genetic c

关 键 词：不良妊娠 隐匿性平衡易位 染色体微阵列分析 荧光原位杂交 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]