DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.
DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study.
复制标题
DOI：
10.1038/gim.2011.73
复制
发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
确定母体血浆无细胞DNA测序能否有效鉴别18三体和13三体。从4，664例妊娠沿着匹配整倍体对照（包括212例已报道的唐氏综合征和匹配对照）中选择62例18三体妊娠和12例13三体妊娠，并使用实验室开发的下一代测序测试对其样品进行测试。对18号和13号染色体结果的解释包括CG含量偏倚的调整。在99.1%的解释样本（1，971/1，988）中，观察到的18三体和13三体检出率分别为100%（59/59）和91.7%（11/12），假阳性率分别为0.28%和0.97%。在17个没有解释的样本中，有3个是18三体。如果18三体和13三体的z评分临界值略有提高，则三种非整倍体的总体假阳性率可低至0.1%（2/1，688），而常见非整倍体的总体检出率为98.9%（280/283）。一个独立的学术实验室证实了一个子集的性能。在高危妊娠中，对循环游离DNA进行测序几乎可以检测到所有唐氏综合征、18三体和13三体的病例，假阳性率很低。这可能会减少95%的侵入性诊断程序和相关的胎儿损失。证据支持这些非整倍体的临床试验。
To determine whether maternal plasma cell–free DNA sequencing can effectively identify trisomy 18 and 13. Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias. Among the 99.1% of samples interpreted (1,971/1,988), observed trisomy 18 and 13 detection rates were 100% (59/59) and 91.7% (11/12) at false-positive rates of 0.28% and 0.97%, respectively. Among the 17 samples without an interpretation, three were trisomy 18. If z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies. An independent academic laboratory confirmed performance in a subset. Among high-risk pregnancies, sequencing circulating cell–free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies.