Zhang Li, Zhu Qian, Wang He, Liu Shanling
West China Second University Hospital, Sichuan UniversityChengdu, Sichuan, China.
The First People's Hospital of ChengduChengdu, Sichuan, China.
Am J Transl Res. 2017 Jul 15;9(7):3469-3473. eCollection 2017.
Our goal was to derive more sensitive and accurate Z-scores based on combined DNA count- and size-based algorithms to advance molecular diagnostics for noninvasive prenatal testing of fetal trisomies.
We included 180 cases at high risk for fetal aneuploidy who underwent amniotic fluid cytogenetic analysis. We calculated their traditional count-based Z-scores, as well as their 100-, 130- and 150-, and 166-bp size-corrected Z-scores, and determined each Z-score's reliability based on its comparison to the cases' cytogenetic results.
We detected for trisomies 13, 18, or 21 among the 180 cases in our study by amniotic testing and DNA sequence analysis. None trisomies 13 was detected, while 1 case of trisomies 18 and 3 cases of trisomies 21 were found. The sensitivity, specificity, and accuracy of traditional count-based Z-scores were 75%, 98.86%, and 98.33%, respectively, while these rates increased to 80%, 99.43%, and 99.44% with a count-based 100- and 166-bp size correction. Moreover, the sensitivity, specificity, and accuracy of count-based Z-scores with 130- and 150-bp size corrections were 100%, and neither of these algorithms yielded false positive trisomies, unlike other evaluated size correction Z-scores.
Count-based Z-scores with 130- and 150-bp size corrections more robustly predict fetal trisomies than count-based methods alone or those combined with other size-correction cutoffs, such as 166 bp. These testing parameters may enhance the utility of DNA sequence-based methods for noninvasive prenatal detection of fetal trisomies.
我们的目标是基于结合DNA计数和大小的算法得出更敏感、准确的Z分数，以推进胎儿三体非侵入性产前检测的分子诊断。
我们纳入了180例胎儿非整倍体高风险病例，这些病例均接受了羊水细胞遗传学分析。我们计算了他们基于传统计数的Z分数，以及100、130、150和166碱基对大小校正后的Z分数，并通过与病例的细胞遗传学结果比较来确定每个Z分数的可靠性。
通过羊水检测和DNA序列分析，我们在研究的180例病例中检测出13、18或21三体。未检测到13三体，而发现1例18三体和3例21三体。基于传统计数的Z分数的敏感性、特异性和准确性分别为75%、98.86%和98.33%，而基于计数的100和166碱基对大小校正后，这些比率分别提高到80%、99.43%和99.44%。此外，基于130和150碱基对大小校正的计数Z分数的敏感性、特异性和准确性均为100%，与其他评估的大小校正Z分数不同，这些算法均未产生假阳性三体。
基于130和150碱基对大小校正的计数Z分数比单独的基于计数的方法或与其他大小校正临界值（如166碱基对）结合的方法更能可靠地预测胎儿三体。这些检测参数可能会提高基于DNA序列的方法在胎儿三体非侵入性产前检测中的效用。
