高通量测序技术检测自然流产绒毛染色体异常的准确性分析

Application of Next Generation Sequencing in Testing the Chromosomal Abnormalities of Spontaneous Abortion Villi

目的:探讨高通量测序技术检测自然流产绒毛染色体异常的准确性。方法:选择2018年3月-2019年3月在本院行自然流产术的39例患者,提取39份绒毛标本,采用高通量测序技术对绒毛组织的基因组DNA进行分析,并与细胞培养染色体核型分析结果进行比较。结果:细胞培养染色体核型分析发现:染色体异常21例(53.85%),染色体未见明显异常14例(35.90%),检测失败4例(10.26%)。在21例染色体异常样本中,非整倍体11例(52.38%),单体共5例(23.81%),四体3例(14.29%),染色体结构异常2例(9.52%)。高通量测序检测发现:染色体异常25例(64.10%),染色体未见明显异常14例(35.90%)。其中细胞培养染色体核型分析未见明显异常的14例标本中,发现1例三体嵌合体、2例拷贝数变化(CNVs);4例检测失败标本中,发现1例CNVs。2种检测方法检出率差异无统计学意义(χ~2=2.250,P=0.134)。结论:高通量测序检测技术是一项有助于明确自然流产遗传学因素的高效遗传学检测手段,可以作为细胞培养染色体核型分析检查的有力补充。

Objective: To investigate the application of next generation sequencing in testing the chromosome abnormalities of spontaneous abortion villus. Methods: Thirty-nine villi samples of spontaneous abortion were extracted for the high-throughput sequencing from March 2018 to March 2019. The classical karyotype analysis was used as the control of high-throughput sequencing. Results: In classical karyotype analysis,chromosome abnormalities were found in 21 cases(53.85%), no obvious abnormality in 14 cases(35.90%), and testing failure occurred in 4 cases(10.26%). Among the 21 chromosome abnormalities, there were 11 aneuploid cases(52.38%), 5 monomer cases(23.81%), 3 tetrasomia cases(14.29%), and 2 cases of chromosome structural abnormalities(9.52%). In the high-throughput sequencing, chromosome abnormalities were found in 25 cases(64.10%), and no obvious chromosome abnormality in 14 cases(35.90%). In those 14 cases, there were 1 trisomy chimera and 2 copy number variations(CNVs). One case of CNVs was found in 4 testing failures. There was no significant difference in the detection rate between the two methods(χ~2=2.250, P=0.134). Conclusions: The highthroughput sequencing is an efficient method to clarify the genetic factors of spontaneous abortion. As a powerful supplement for classical karyotype analysis, it is worthy of clinical promotion and wide application.