高通量测序在自然流产遗传学诊断中的应用

Application of next generation sequencing for the analysis of patients with spontaneous abortion

目的应用高通量测序（next generation sequencing，NGS）技术检测染色体非整倍体改变和拷贝数变异，探讨其在自然流产遗传学诊断中的应用价值。方法对孕42天至12周自然流产的绒毛组织进行核型分析，对核型分析结果无异常、培养失败和难以确诊的85例样本应用高通量测序检测。结果NGS在核型分析无异常的68例样本中检测出2例拷贝数变异、2例嵌合；在16例培养失败的样本中检测出1例拷贝数异常、3例染色体数目异常；将1例常规核型分析结果不明确的样本确诊为46，XX，del（4）（p15．1p16．3）．seq[GRCh37／hg19]（57549—32371364）×1。结论测序技术能够在核型分析结果无异常的样本中检测出拷贝数变异，对培养失败和难以确诊的病例进行明确诊断。

Objective To assess the value of next generation sequencing （NGS） for the analysis of spontaneous abortion samples. Methods The NGS analysis was carried out on 85 ehorionic villi samples （taken between 42 days to 12 weeks of gestation） for which conventional cell culture has failed or chromosomal karyotyping has yielded normal or uncertain result. Results Among 68 samples with a normal karyotype, the NGS analysis has identified 2 copy number variations （CNVs） and 2 chimeras. For 16 cases with failed cell culture, the NGS has identified 4 chromosomal abnormalities including 1 copy number variation and 3 numerical chromosomal aberrations. For 1 remaining case with uncertain karyotyping result, the NGS analysis has verified it as 46,XX,del（4） （p15. lp16.3）, seq[GRCh37/hg19] （57 549 - 32 371 364） × 1. Conclusion The NGS analysis is capable of identifying novel CNVs in samples for which conventional cell culture may fail or karvotyping analvsis mav yield a normal result.