Rosenfeld Jill A, Morton S Anne, Hummel Cathryn, Sulpizio Scott G, McDaniel Lisa D, Schultz Roger A, Torchia Beth S, Ravnan J Britt, Ellison Jay W, Fisher Allan J
Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Wash., USA.
Fetal Diagn Ther. 2014;36(3):231-41. doi: 10.1159/000360081. Epub 2014 Aug 8.
While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS).
We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis.
Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis.
When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification.
虽然微阵列检测能够识别核型分析遗漏的染色体异常，但由于可能会识别出意义不明确的变异（VOUS），其在低风险妊娠中的产前应用通常被避免。
我们使用基于珠子的快速BAC检测法，对2970份所有转诊指征的产前样本进行检测，该检测法使用了针对性染色体、常见常染色体非整倍体以及20种微缺失/微重复综合征的探针，设计该检测法是为了在低风险妊娠中替代微阵列检测，以及在同时进行微阵列分析的妊娠中替代快速非整倍体检测。
2940例（99.0%）获得了可解释的结果，89%在1天内得到结果。检测到7.3%的非整倍体和0.45%（n = 13）的部分染色体异常，其中5例是因孕妇年龄、孕妇血清筛查异常或孤立性超声标志物转诊。在超声正常或孤立性超声标志物/颈项透明层测量值增加的低风险病例中，高于核型分析的额外检测率为1/745，在有结构/生长异常的胎儿中为1/165。在检测限度内未发现假阴性或假阳性。无法检测到女性多倍体，而怀疑存在带有Y染色体的多倍体，并通过进一步分析得以证实。
当与核型分析结合使用时，该检测法可增加对特定染色体区域的检测，同时限制VOUS的识别。
