应用有向游离 DNA 分析检测胎儿性染色体非整倍体。

Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA analysis.

机构信息

Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.

出版信息

Fetal Diagn Ther. 2014;35(1):1-6. doi: 10.1159/000357198. Epub 2013 Dec 11.

DOI:10.1159/000357198

PMID:24335155

Abstract

OBJECTIVE

To examine the performance of chromosome-selective sequencing of cell-free (cf) DNA in maternal blood for assessment of fetal sex chromosome aneuploidies.

METHODS

This was a case-control study of 177 stored maternal plasma samples, obtained before fetal karyotyping at 11-13 weeks of gestation, from 59 singleton pregnancies with fetal sex chromosome aneuploidies (45,X, n = 49; 47,XXX, n = 6; 47,XXY, n = 1; 47,XYY, n = 3) and 118 with euploid fetuses (46,XY, n = 59; 46,XX, n = 59). Digital analysis of selected regions (DANSR™) on chromosomes 21, 18, 13, X and Y was performed and the fetal-fraction optimized risk of trisomy evaluation (FORTE™) algorithm was used to estimate the risk for non-disomic genotypes. Performance was calculated at a risk cut-off of 1:100.

RESULTS

Analysis of cfDNA provided risk scores for 172 (97.2%) samples; 4 samples (45,X, n = 2; 46,XY, n = 1; 46,XX, n = 1) had an insufficient fetal cfDNA fraction for reliable testing and 1 case (47,XXX) failed laboratory quality control metrics. The classification was correct in 43 (91.5%) of 47 cases of 45,X, all 5 of 47,XXX, 1 of 47,XXY and 3 of 47,XYY. There were no false-positive results for monosomy X.

DISCUSSION

Analysis of cfDNA by chromosome-selective sequencing can correctly classify fetal sex chromosome aneuploidy with reasonably high sensitivity.

摘要

目的

研究母体外周血游离（cf）DNA 染色体选择测序在胎儿性染色体非整倍体评估中的应用。

方法

本研究为病例对照研究，共纳入 177 例在妊娠 11-13 周行胎儿核型分析前采集的母体外周血储存样本，这些样本来源于 59 例胎儿性染色体非整倍体（45,X，n=49；47,XXX，n=6；47,XXY，n=1；47,XYY，n=3）和 118 例胎儿核型正常（46,XY，n=59；46,XX，n=59）的单胎妊娠孕妇。对 21、18、13、X 和 Y 染色体的选定区域（DANSR™）进行数字分析，并采用胎儿分数优化的三体评估（FORTE™）算法估计非整倍体基因型的风险。以 1:100 的风险截断值计算检测性能。

结果

对 172 例（97.2%）样本进行了 cfDNA 分析，提供了风险评分；4 例（45,X，n=2；46,XY，n=1；46,XX，n=1）因胎儿 cfDNA 分数不足无法进行可靠检测，1 例（47,XXX）实验室质量控制指标失败。47 例 45,X 中 43 例（91.5%）的分类正确，5 例 47,XXX、1 例 47,XXY 和 3 例 47,XYY 也均正确分类。X 单体性无假阳性结果。