全外显子组测序技术在超声指标异常胎儿遗传病中应用价值分析  

Application of the Appliation Value of Whole Exome Sequencing Technology in Fetal Genetic Diseases with Abnormal Ultrasound Indicators

作　　者：胡兰萍[1] 彭灿 林彭思远 卜秀芬 江璇宇 周世豪[1] 李红玉[1] 王卫红[1] 贺骏[1] HU Lanping;PENG Can;LINPENG Siyuan(Prenatal Diagnosis Center of Changsha Maternal and Child Health Hospital,Changsha Hunan 410007,China)

机构地区：[1]长沙市妇幼保健院产前诊断中心,湖南长沙410007

出　　处：《实用妇产科杂志》2023年第9期692-695,共4页Journal of Practical Obstetrics and Gynecology

摘　　要：目的:探讨全外显子组测序(WES)技术在超声指标异常,但染色体核型分析及染色体微阵列(CMA)检测结果阴性胎儿中的临床应用价值。方法:回顾性分析2018年6月至2021年4月在长沙市妇幼保健院产前超声检查中发现超声指标异常胎儿1080例,对胎儿羊水或脐血进行CMA检测和染色体核型分析,并对部分染色体核型分析及CMA结果阴性胎儿进行WES检测,所有变异等级根据美国医学遗传学和基因组学学会遗传变异分类标准与指南进行分类。结果:1080例胎儿全部经过CMA检测,其中947例同时进行了染色体核型分析,CMA检测到136例拷贝数变异(CNV),检出率12.6%(136/1080),其中85例致病性CNV、51例致病意义未明。染色体核型分析共检出91例阳性,检出率9.6%(91/947),其中非整倍体变异54例,结构变异9例,染色体正常变异28例。另外对18例染色体核型分析和CMA检测阴性样本进行WES检测,结果显示5例(27.8%)致病性基因变异,5例可能致病性基因变异,3例意义未明变异,5例未发现异常。结论:在染色体核型分析和CMA检测未能明确超声指标异常胎儿遗传学病因的情况下,WES有助于提高其额外诊断率,为胎儿的诊断及家系的遗传咨询提供依据。Objective:To investigate the clinical application value of whole exome sequencing(WES)in fetuses with abnormal ultrasound indicators but negative chromosomal karyotype analysis and chromosomal microarray(CMA)results.Methods:A retrospective analysis was conducted on 1080 fetuses with abnormal ultrasound indicators found during prenatal ultrasound examinations at Changsha Maternal and Child Health Hospital from June 2018 to April 2021.CMA and chromosomal karyotype analysis were performed on fetal amniotic fluid or cord blood,and WES was performed on some fetuses with negative karyotypes and CMA results.All variant grades were classified according to the guidelines of the American College of Medical Genetics and Genomics.Results:All 1080 fetuses underwent CMA testing,of which 947 underwent chromosome karyotype analysis.136 copy number variations(CNV)were detected by CMA,with a detection rate of 12.6%(136/1080),including 85 cases of pathogenic CNV and 51 cases of unknown significance.A total of 91 positive cases were detected in chromosome karyotype analysis,with a detection rate of 9.6%(91/947),including 54 cases of aneuploidy variation,9 cases of structural variation,and 28 cases of normal chromosomal variation.Furthermore,WES was used to test 18 samples with negative chromosomal karyotype analysis and CMA,and the results showed 5 cases(27.8%)of pathogenic gene variations,5 cases of likely pathogenic gene variations,3 cases of unknown significance variations,and 5 cases of no abnormalities.Conclusions:This study demonstrates that WES can help to improve the additional diagnosis rate when chromosomal karyotype analysis and CMA tests fail to identify the genetic etiology of abnormal fetal ultrasound indicators,as well as provide a foundation for fetal diagnosis and genetic counseling for families.

关 键 词：超声指标异常 全外显子组测序 染色体核型分析 染色体微阵列分析 

分 类 号：R714.55[医药卫生—妇产科学]