6例9p24区微缺失胎儿的产前诊断与遗传学分析  

Prenatal diagnosis and genetic analysis of 9p24 microdeletion in six fetuses

作　　者：吴东[1] 张倩[1] 高越[1] 张梦汀 王凤阳 王鑫[1] 康冰[1] 廖世秀[1] Wu Dong;Zhang Qian;Gao Yue;Zhang Mengting;Wang Fengyang;Wang Xin;Kang Bing;Liao Shixiu(Institute of Medical Genetics of Henan Provincial People's Hospital,Medical Genetic Institute of Henan Province,Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics,National Health Commission Key Laboratory of Birth Defects Prevention,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院医学遗传研究所,河南省医学遗传研究所,河南省遗传性疾病功能基因组重点实验室,国家卫生健康委出生缺陷预防重点实验室,郑州450003

出　　处：《中华围产医学杂志》2022年第2期117-121,共5页Chinese Journal of Perinatal Medicine

基　　金：河南省科技攻关项目(182102310503);河南省医学科技攻关项目(2018020393,LHGJ20200006)。

摘　　要：目的对6例9p24区微缺失的胎儿进行产前诊断与遗传学分析。方法回顾性分析2018年1月至2020年1月因血清学唐氏综合征筛查高风险/临界高风险就诊于河南省人民医院遗传咨询门诊6例孕妇的遗传学检测资料。采用常规G显带和微阵列比较基因组杂交(array comparative genomic hybridization,aCGH)技术检测胎儿羊水及其父母的外周血,对检出的拷贝数变异致病性采用美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)评分标准进行分级。对结果进行描述性分析。结果6例胎儿孕中期超声检查均未发现异常。G显带分析结果显示,6例胎儿及其父母染色体核型分析均未见异常。aCGH检测结果显示,6例胎儿在9p24区存在1019~6001 kb染色体缺失,涉及DMRT1、SMARCA2和DOCK8等疾病相关基因;其中例3胎儿的缺失遗传自无临床表型父亲,其他胎儿染色体缺失为新发突变。参考ACMG分级指南,例1~2、5~6胎儿检出微缺失为致病性/可能致病性,例3和4胎儿检出微缺失为临床意义未明。经遗传咨询后,例1~2、5~6孕妇及家属选择终止妊娠;例3和4选择继续妊娠,出生后半年随访婴儿发育良好。结论9p24区微缺失胎儿产前缺乏特异性表型,DMRT1和SMARCA2可能为该区域关键基因。Objective To investigate the prenatal diagnosis and genetic analysis of 9p24 microdeletion in six fetuses.Methods Genetic data of six pregnant women with positive results of serological Down's syndrome screening at Henan Provincial People's Hospital from January 2018 to January 2020 were retrospectively collected and analyzed.Amniotic fluid and the parents'peripheral blood samples were subjected to G banding and array comparative genomic hybridization(aCGH)analysis.Detected copy number variation(CNV)were classified based on the American College of Medical Genetics and Genomics(ACMG)scoring standard.Results Six fetuses showed no abnormalities in ultrasound during the second trimester as well as in karyotyping.A chromosome deletion of 1019~6001 kb at 9p24 was found in all six fetuses by aCGH,referring to disease-related genes DMRT1,SMARCA2,DOCK8,etc.The deletion of case 3 was inherited from the asymptomatic father,and the other fetal five were all de novo mutations.Cases 1,2,5,and 6 were pathogenic/likely pathogenic CNV carriers and cases 3 and 4 were CNV of unknown clinical significance carriers.After genetic counseling,cases 1,2,5,and 6 chose to terminate the pregnancies;cases 3 and 4 continued and gave birth to normal offspring.Conclusions Fetuses with 9p24 microdeletion lack specific phenotypes before born.DMRT1 and SMARCA2 may be the key genes in this region.

关 键 词：染色体 人 9对 染色体缺失 微阵列比较基因组杂交 DNA拷贝数变异 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学]