染色体微阵列分析技术在759例不同产前诊断指征孕妇羊水中的临床应用分析

Clinical application of chromosome microarray analysis in the amniotic fluid of 759 pregnant women with different prenatal diagnosis indications

目的探讨染色体微阵列分析技术(CMA)在不同产前诊断指征中的临床应用分析,以期促进临床医生对羊水诊断指征的准确把握,提高诊断效率。方法回顾性分析本院2016年1月至2019年9月共759例产前羊水样本的CMA检测结果,分析阳性诊断率与不同产前诊断指征的相关性。结果759例产前羊水共检出126例致病病例,异常检出率为16.6%。其中大片段(≥10 Mb)及非整倍体异常致病病例85例,CMA与传统核型分析(≥10 Mb)检出一致;此外,CMA可多检出5.3%(40/759)的小片段异常致病病例。不同羊水穿刺指征的CMA阳性检出率最高为无创产前DNA检测(NIPT)高风险(28.9%),其次为B超异常(12.5%)。在344例B超异常样本中脑部异常(21.7%)、肠管异常(21.4%)和胎儿颈部透明带(NT)异常(20.9%)的CMA检出率较高。在随访的260例病例中,非整倍体异常病例40例,占比15.4%;致病性拷贝数变异(PCNV)病例13例,占比5.0%;临床意义未明变异(VOUS)病例39例,占比15.0%。结论CMA在传统核型分析(≥10 Mb)的基础上进一步提高染色体异常的检出率;结合B超异常分类,应慎重把握行侵入性产前诊断的临床指征;CMA检测结果为VOUS的患者需充分做好遗传咨询。

Objective:To explore the application of chromosome microarray analysis(CMA)in different prenatal diagnosis indications,in order to promote the accurate grasp of diagnostic indicators of amniotic fluid by clinicians,and improve the diagnostic efficiency.Methods:The CMA results of 759 prenatal amniotic fluid samples in our hospital from January 2016 to September 2019 were retrospectively analyzed to find the correlation between the positive diagnosis rate and different prenatal diagnosis indicators.Results:A total of 126 pathogenic cases were detected in 759 prenatal samples,with an abnormal detection rate of 16.6%.85 cases with large fragments(≥10 Mb)and aneuploidy were detected,and CMA was consistent with the traditional karyotype analysis(≥10 Mb).In addition,CMA could detect 5.3%(40/759)more cases of small fragment abnormalities.The highest positive detection rate(28.9%)of different clinical indications was non-invasive prenatal testing(NIPT)with high risk,followed by abnormal B-ultrasound(12.5%).The detection rate of brain abnormalities(21.7%),bowel abnormalities(21.4%)and nuchal translucency(NT)abnormalities(20.9%)was highest in 344 patients with abnormal B-ultrasound.Among the 260 patients followed up,40 patients were aneuploidy,accounting for 15.4%;13 patients were pathogenic copy number variation(CNV),accounting for 5%;39 patients were clinically unknown(VOUS),accounting for 15%.Conclusions:CMA further improves the detection rate of chromosomal abnormalities on the basis of traditional karyotype analysis(≥10 Mb).Combined with the classification of B-ultrasound abnormalities,the clinical indications of invasive prenatal diagnosis should be carefully grasped.Patients with VOUS results need adequate genetic counseling.