Cytogenetics Laboratory, Laboratory Corporation of America® Holdings, Research Triangle Park, NC, 27709, USA.
Integrated Genetics, LabCorp Specialty Testing Group, 655 Huntington Drive, Monrovia, CA, 91016, USA.
Prenat Diagn. 2018 Feb;38(3):210-218. doi: 10.1002/pd.5217. Epub 2018 Feb 26.
Screening via noninvasive prenatal testing (NIPT) involving the analysis of cell-free DNA (cfDNA) from plasma has become readily available to screen for chromosomal and DNA aberrations through maternal blood. This report reviews a laboratory's experience with follow-up of positive NIPT screens for microdeletions.
Patients that were screened positive by NIPT for a microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies by either chorionic villus sampling or amniocentesis were evaluated.
The overall positive predictive value for 349 patients was 9.2%. When a microdeletion was confirmed, 39.3% of the cases had additional abnormal microarray findings. Unrelated abnormal microarray findings were detected in 11.8% of the patients in whom the screen positive microdeletion was not confirmed. Stretches of homozygosity in the microdeletion were frequently associated with a false positive cfDNA microdeletion result.
Overall, this report reveals that while cfDNA analysis will screen for microdeletions, the positive predictive value is low; in our series it is 9.2%. Therefore, the patient should be counseled accordingly. Confirmatory diagnostic microarray studies are imperative because of the high percentage of false positives and the frequent additional abnormalities not delineated by cfDNA analysis.
通过分析母体血浆中的游离细胞 DNA（cfDNA）进行非侵入性产前检测（NIPT）已广泛应用于通过母血筛查染色体和 DNA 异常。本报告回顾了实验室对 NIPT 阳性筛查微缺失的随访经验。
对经 NIPT 筛查出 1p、4p、5p、15q 或 22q 微缺失且接受绒毛膜绒毛取样或羊膜穿刺术进行诊断研究的患者进行评估。
349 例患者的总体阳性预测值为 9.2%。当微缺失得到证实时，39.3%的病例有额外的异常微阵列发现。在未证实筛查阳性微缺失的患者中，有 11.8%检测到无关的异常微阵列发现。微缺失中的纯合区域常与 cfDNA 微缺失结果的假阳性有关。
总的来说，本报告表明，虽然 cfDNA 分析可以筛查微缺失，但阳性预测值较低；在我们的研究中为 9.2%。因此，应相应地对患者进行咨询。由于假阳性率高，且 cfDNA 分析常不能明确的额外异常，因此必须进行确认性诊断微阵列研究。
