应用高通量测序技术检测74例早期自然流产绒毛染色体结果分析

Analysis on chromosomal detection results of chorionic villi in 74 patients with early spontaneous abortion using high-throughput sequencing technology

目的 应用高通量测序技术检测早期自然流产绒毛组织染色体,探讨早期自然流产的遗传学病因。方法 高通量测序检测74例早期自然流产孕妇(孕40~77 d)的绒毛组织,统计染色体异常的类型及所占比率。根据患者是否通过辅助生殖技术(ART)受孕将其分为ART组24例和自然妊娠组50例。结果 74例早期自然流产患者绒毛组织中,染色体异常46例(62.16%);染色体数目异常41例,其中三体型占44.59%(33/74),X单体占6.76%(5/74),嵌合体占4.05%(3/74)。染色体结构异常5例占6.76%(5/74),其中3例重复(1例致病性,2例临床意义不明),2例缺失(1例致病性,1例临床意义不明)。孕妇年龄≥35岁组和<35岁组的绒毛染色体异常率分别为64.71%(11/17)和61.40%(35/57),两组比较差异无统计学意义(P>0.05)。复发性流产(RSA)组42例,其中绒毛染色体异常24例(57.14%),偶发流产组32例,其中绒毛染色体异常22例(68.75%),两组比较差异无统计学意义(P>0.05)。ART组绒毛染色体异常14例,自然妊娠组绒毛染色体异常32例,两组比较差异无统计学意义(P>0.05)。结论 染色体异常是早期自然流产的重要原因,高龄、复发性流产及辅助生殖技术助孕是否增加胚胎染色体异常发生率尚不明确。高通量测序技术应用于绒毛染色体检测对于分析早期自然流产的原因具有重要意义,为临床医师给患者提供合理的优生遗传咨询提供基础。

Objective To detect chromosome of chorionic villi of early spontaneous abortion using high-throughput sequencing technology, explore the genetic pathogenesis of early spontaneous abortion. Methods High-throughput sequencing technology was used to detect chorionic villi of 74 patients with early spontaneous abortion(40-77 days), the types and proportions of chromosomal abnormalities were analyzed. According to using assisted reproductive technology(ART) or not, the patients were divided into ART group(24 cases) and spontaneous pregnancy group(50 cases). Results Among 74 patients with early spontaneous abortion, 46 patients(62.16%) were diagnosed as chromosomal abnormalities, 41 patients were found with chromosomal numerical abnormality, the proportions of trisomy syndrome, X chromosome monomer, and chimera were 44.59%(33/74), 6.76%(5/74), and 4.05%(3/74), respectively, 5 patients were found with chromosomal structural abnormality, accounting for 6.76%(5/74), including 3 patients with chromosome duplication(one patient with pathogenicity and two patients of unknown clinical significance) and 2 patients with chromosomal deletion(one patient with pathogenicity and one patient of unknown clinical significance). The incidence rates of chromosomal abnormalities in ≥35-year-old group and <35-year-old group were 64.71%(11/17) and 61.40%(35/57), respectively, there was no statistically significant difference between the two groups(P>0.05). Among 42 patients with recurrent spontaneous abortion, the incidence rate of chromosomal abnormalities was 57.14%(24 cases), among 32 patients with sporadic abortion, the incidence rate of chromosomal abnormalities was 68.75%(22 cases), there was no statistically significant difference between the two groups(P>0.05). In ART group, 14 patients were diagnosed as chromosomal abnormalities, in spontaneous pregnancy group, 32 patients were diagnosed as chromosomal abnormalities, there was no statistically significant difference between the two groups(P>0.05). Conclusion Chromosomal abnormality is an important cause of early spontaneous abortion. It is uncertain whether advanced maternal age, recurrent spontaneous abortion, and ART increase the risk of chromosomal abnormality in embryos. The application of high-throughput sequencing technology to villous chromosomal detection is of great significance for analysis of the causes of early spontaneous abortion, which can provide a basis for reasonable eugenic and genetic counseling.