高通量测序技术在提高胎儿颈项透明层增厚染色体致病性检出率中的应用价值

Application value of high-throughput sequencing technology in improving t he pathogenicity detection rate of fetal cervical transparent layer thickened chromosome

目的:探讨高通量测序技术在提高胎儿颈项透明层增厚染色体致病性检出率中的应用价值。方法:收集2021年1月到2021年12月在河北医科大学第二医院产前诊断中心因孕11~13^(+6)周超声提示胎儿颈项透明层(NT)增厚而进行进一步检查的60例孕妇的临床资料,按NT厚度将其分为2.5 mm≤NT<3.0 mm组(23例)、3.0 mm≤NT<3.5mm组(18例)、3.5mm≤NT<4.0 mm组(3例)、NT≥4.0 mm组(16例)。采用孕中期抽取羊水法对各组孕妇进行胎儿染色体核型分析和染色体拷贝数变异检测(采用高通量基因测序技术),观察分析相关结果。结果:胎儿染色体核型分析结果:染色体异常7例,6例为21三体,1例为8号染色体异常,异常率为11.67%。高通量基因测序检测结果:染色体异常29例,异常率为48.33%。6例为21三体,1例为8号染色体重复18.08Mb,染色体微缺失微重复22例。其中致病性微重复1例,致病性微缺失1例,致病携带者微缺失1例,疑似致病微缺失1例,临床意义未明微缺失微重复18例。2.5 mm≤NT<3.0 mm组(23例)检出核型异常2例,核型异常率8.70%;检出拷贝数异常10例,拷贝数异常率43.48%。3.0mm≤NT<3.5mm组(18例)检出核型异常2例,核型异常率11.11%;检出拷贝数异常10例,拷贝数异常率55.56%。3.5mm≤NT<4.0 mm组(3例)检出核型异常0例,核型异常率0%;检出拷贝数异常0例,拷贝数异常率0%。NT≥4.0 mm组(16例)检出核型异常3例,核型异常率18.75%;检出拷贝数异常9例,拷贝数异常率56.25%。结论:胎儿NT增厚与染色体非整倍体异常有密切关系,也与一些染色体拷贝数变异有关。随着NT厚度的增加,胎儿染色体的异常率也会相应增加。高通量测序技术可以在全基因组范围内检测出一些明确致病性的微缺失微重复,提高染色体异常的检出率,从而减少高度致残胎儿的出生,减轻家庭和社会的负担。

Objective:To investigate the application value of high-throughput sequencing technology in improving the pathogenicity detection rate of fetal cervical transparent layer thickened chromosome.Method:Clinical data of 60 pregnant women who underwent further examination at Prenatal Diagnosis Center of the Second Hospital of Hebei Medical University from January 2021 to December 2021 due to ultrasonography at 11~13^(+6) weeks of gestation indicating thickening of the clear layer of fetal neck(NT)were collected.According to NT thickness,they were divided into 2.5 mm≤NT<3.0 mm group(23 cases),3.0 mm≤NT<3.5mm group(18 cases),3.5mm≤NT<4.0 mm group(3 cases),and NT≥4.0 mm group(16 cases).Fetal chromosome karyotype analysis and chromosome copy number variation detection were performed by amniotic fluid extraction during the second trimester(high-throughput gene sequencing technology was adopted),and relevant results were observed and analyzed.Results:There were 7 cases of chromosome abnormality,6 cases of trisomy 21,1 case of chromosome 8 abnormality,the abnormal rate was 11.67%.Results of high-throughput gene sequencing:29 cases with chromosome abnormality,the abnormal rate was 48.33%.There were 6 cases of trisomy 21,1 case of chromosome 8 duplication 18.08Mb,and 22 cases of chromosome microdeletion and microduplication.Among them,there were 1 pathogenic microdeletion,1 pathogenic microdeletion,1 carrier microdeletion,1 suspected pathogenic microdeletion,and 18 microdeletion microduplication of unknown clinical significance.In the 2.5mm≤NT<3.0mm group(23 cases),abnormal karyotype was detected in 2 cases,the abnormal karyotype rate was 8.70%.Ten abnormal copy number cases were detected,and the abnormal copy number rate was 43.48%.Abnormal karyotype was detected in 2 cases(18 cases)of 3.0mm≤NT<3.5mm group,and the abnormal karyotype rate was 11.11%.Ten abnormal copy numbers were detected,with an abnormal copy number rate of 55.56%.In the 3.5mm≤NT<4.0mm group(3 cases),0 cases of abnormal karyotype were detected,and the abnormal karyotype rate was 0%.0 abnormal copy number cases were detected,and the abnormal copy number rate was 0%.Abnormal karyotype was detected in 3 cases(16 cases)in NT≥4.0mm group(18.75%).Abnormal copy number was detected in 9 cases,with an abnormal copy number rate of 56.25%.Conclusion:Fetal NT thickening is closely related to chromosome aneuploidy abnormality and some chromosome copy number variation.With the increase of NT thickness,the abnormal rate of fetal chromosomes also increased.High-throughput sequencing technology can detect some clearly pathogenic microdeletions and microduplicates within the whole genome,improve the detection rate of chromosomal abnormalities,and thus reduce the birth of highly disabled fetuses and reduce the burden on families and society.