二代测序技术检测早期自然流产胚胎染色体异常

目的探讨二代测序（NGS）技术检测早期自然流产（SA）绒毛组织染色体异常的价值。方法选择自然流产患者87 例，其中复发性流产32 例，偶发性流产55 例。年龄≥35 岁组35 例，<35 岁组52 例。取其流产绒毛组织，行NGS 全基因组测序及G 显带染色体核型分析，比较2 种方法的检测成功率和异常检出率，比较不同流产类型及不同年龄患者的流产组织染色体异常率。结果NGS 技术检测流产绒毛组织的成功率(100.00%)高于G 显带核型 (74.71%)，异常检出率(58.62%)也高于G 显带核型（50.77%）。NGS 检测的51 例异常中染色体结构异常3 例（5.88%），染色体数目异常48 例（94.12%），其中三体39 例，双重三体2 例，三重三体1 例，单体6 例。G 显带核型分析检出的33 例异常中染色体数目异常32 例，其中三体24 例，双重三体2 例，三重三体1 例，单体5 例；染色体结构异常1 例。NGS 与G 显带核型分析测序结果相符64 例，不符1 例。NGS 技术检测偶发性流产与复发性流产组织染色体异常率分别是60.00%和56.25%，差异无统计学意义。≥35 岁组的染色体异常率（71.43%）高于<35 岁组（50.00%），差异有统计学意义（P < 0.05）。结论NGS 技术检测染色体异常的分辨率好，准确度高，有助于明确SA 的病因，指导患者再次妊娠及优生优育。

Detection of chromosome abnormality by next-generation sequencing technology of miscarried embryo in the first-trimester

Objective To investigate the clinical values of next-generation sequencing (NGS) technology in diagnosis of miscarried chorionic villi genetic disorders. Methods Patients who underwent miscarriage (n=87) were enrolled in this study. Among all patients, 32 cases were of recurrent miscarrage and 55 cases were of sporadic miscarriage. In all collected patients, 35 women were 35 years or older while other 52 women were less than 35 years old. Positive detection rate and the abnormal detection rate were compared between these two methods. Chromosomes abnormal rates were also compared among different types of miscarrage and different ages. All aborted villi tissue were analyzed by NGS of whole genome and G-band? ing karyotype. Results The successful detection rate of chorionic villi by NGS (100.00%) was higher than that of G-band? ing karyotype (74.71%), and the detection rate of abnormal chorionic villi by NGS (58.62%) was also higher than that of Gbanding karyotype (50.77%). Three cases of chromosome structure anomaly were found in those 51 chromosome anomalies (5.88%). Other 48 cases of chromosome anomalies were aneuploidy anomalies (94.12%) include 39 cases of trisomy, 2 cases of double trisomy and 1 case of triple trisomy and 6 cases of monomer. On the other hand, 32 cases of chromosome aneuploi? dy anomalies were found in 33 chromosome anomalies by G-banding karyotype, which include 24 cases of trisomy, 2 cases of double trisomy, 1 case of triple trisomy, 5 cases of monomer and 1 case of chromosome structure anomaly. Most NGS re? sults (n=64) were in agreement with G-banding karyotype but with 1 case of discrepancy. Chromosomal abnormality rate de? tected by NGS in sporadic miscarrage group and recurrent spontaneous miscarrage group were 60.00％and 56.25％respective? ly. There was no significant difference (P > 0.05). Chromosomal abnormality rate picked by NGS in women aged ≥35 years old (71.43％) was higher than that in women <35 years old (50.00%) with statistically significant difference (P < 0.05). Conclu? sion NGS technology showed highly accuracy in detecting chromosomal abnomality from villi tissue. Therefore, it could help to detect genetic disorders of miscarrage. It is useful to determine the reasons of miscarrage and guide the next pregnancy.