摘要
目的探讨染色体核型分析、基因组拷贝数变异测序(CNV-seq)和全外显子组测序(WES)在胼胝体异常(CCA)胎儿产前诊断中的应用价值。方法2015年7月—2023年12月郑州大学第一附属医院经超声或MRI诊断为CCA胎儿的孕妇39例,观察胎儿颅脑发育情况及合并颅外其他异常情况。采集羊水样本,14例行染色体核型分析,39例行CNV-seq。染色体核型分析和CNV-seq检测结果为临床意义未明和正常胎儿34例中6例行核心家系全外显子组测序(trio-WES)。对39例CCA胎儿随访至出生后6~12个月,记录妊娠结局。结果39例CCA胎儿中,胼胝体完全缺如2例,胼胝体部分缺如15例,胼胝体发育不良22例;孤立型CCA 13例,复杂型CCA 26例;合并其他异常中以颅脑异常最多,其中侧脑室增宽13例,透明隔腔异常14例。14例行染色体核型分析,检出21-三体1例(7.1%),染色体核型正常13例。39例行CNV-seq,检出CCA相关致病性拷贝数变异(CNV)4例(10.3%),临床意义未明CNV 2例,CNV正常33例。6例行trio-WES,检出CCA相关致病性突变2例(33.3%)。随访结果显示,13例孤立型CCA中出生9例,引产1例,失访3例;26例复杂型CCA中出生2例,引产12例,失访12例。染色体核型异常1例、致病性CNV 2例、临床意义未明CNV 1例、trio-WES检出CCA相关致病性突变2例胎儿均引产;trio-WES阴性4例中出生3例,引产1例。结论对超声或MRI诊断的CCA胎儿,CNV-seq可作为一线检测技术用于筛查遗传学病因;CNV-seq结果为阴性或临床意义未明CNV时,建议行trio-WES,可提高CCA胎儿的致病性突变检出率,有助于妊娠决策及胎儿出生后发育预测。
Objective To investigate the application values of chromosome karyotype analysis,copy number variation sequencing(CNV-seq)and whole exome sequencing(WES)to the prenatal diagnosis of fetuses with corpus callosum anomalies(CCA).Methods Thirty-nine fetuses were diagnosed with CCA by ultrasound and/or MRI in the First Affiliated Hospital of Zhengzhou University from July 2015and December 2023,and the brain and other extracranial anomalies were observed.The amniotic fluid samples were collected to perform karyotype analysis in 14fetuses and CNV-seq in 39.In 34variants of uncertain significance and normal fetuses from karyotype analysis and CNV-seq,6fetuses were performed trio-WES.All 39fetuses with CCA were followed up till 6to 12months after birth to record the pregnancy outcomes.Results Among 39CCA fetuses,there were 2cases of complete agenesis,15cases of partial agenesis,and 22cases of dysgenesis of the corpus callosum;13were isolated CCA,and 26were complex CCA.The most common co-occurring anomalies were brain abnormalities,including 13cases of enlarged lateral ventricles and 14cases of cavum septipellucidi anomalies.The karyotype analysis results of 14fetuses with CCA identified 1case(7.1%)of trisomy 21,and 13cases of normal karyotype.CNV-seq results of 39fetuses confirmed CCA-related pathogenic CNVs in 4cases(10.3%),2cases of variants of uncertain significance CNV,and 33cases of normal CNV.Trio-WES results of 6 cases identified CCA-related pathogenic mutations in 2cases(33.3%).The follow-up results showed that among these 13 isolated CCA cases,there were 9of born alive and 1of induced abortion,and 3were lost to follow up;among these 26 complex CCA cases,there were 2of born alive and 12of induced abortion,and 12were lost to follow up.There was 1 case of chromosomal karyotype abnormality,2cases of pathogenic CNVs,1case of variants of uncertain signicance CNV and 2fetuses of pathogenic mutations detected by trio-WES who were performed induced abortion;among 4cases with negative trio-WES,3were born alive,and 1was performed induced abortion.Conclusions CNV-seq can be used as a first-line detection technique to screen genetic causes for CCA fetuses diagnosed by ultrasound or MRI.For those with variants of uncertain significance and normal fetuses from CNV-seq,trio-WES is suggested,and it can improve the detection rate of pathogenic mutation of CCA fetuses and contributes to pregnancy decision-making and fetal development prediction after birth.
作者
侯雅勤
时盼来
朱晓帆
陈铎
孔祥东
HOU Yaqin;SHI Panlai;ZHU Xiaofan;CHEN Duo;KONG Xiangdong(Genetic and Prenatal Diagnostic Center,the First People’s Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)
出处
《中华实用诊断与治疗杂志》
2024年第12期1196-1202,共7页
Journal of Chinese Practical Diagnosis and Therapy
基金
国家重点研发计划项目(2018YFC1002203)。
关键词
胼胝体异常
全外显子组测序
基因组拷贝数变异测序
染色体核型分析
胎儿
corpus callosum anomalies
whole exome sequencing
copy number variation sequencing
chromosome karyotype analysis
fetus
