University of Women's Hospital, Department of Biomedicine, Basel, Switzerland.
Reprod Biomed Online. 2009 Nov;19(5):714-20. doi: 10.1016/j.rbmo.2009.09.005.
Preimplantation genetic diagnosis (PGD) is usually used to establish a non-affected pregnancy for those couples facing a genetic risk of having an affected child. However, an invasive test is still recommended to all PGD patients due to the risk of misdiagnosis. The discovery of cell-free fetal DNA in maternal plasma provides the possibility for noninvasive prenatal diagnosis. Studies have shown that fetal single-gene disorders can be detected in cell-free fetal DNA by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single-allele base extension reaction (SABER) approach or by the size-fractionation approach, whereby cell-free fetal DNA is enriched on the basis of its smaller size compared with maternal DNA fragments. Recent studies have indicated that a combination of the two approaches increases the accuracy of detection. This study combined the two methods and examined fetal paternally inherited gene mutations in maternal plasma obtained from four PGD-conducted pregnancies. The presence or absence of mutations was correctly detected in all cases. This combined method could be used for risk-free prenatal diagnosis of diseases caused by single-gene mutations, and in particular for couples who undergo PGD who opt not to perform invasive prenatal confirmation due to the risk of abortion.
胚胎植入前遗传学诊断（PGD）通常用于为那些面临生育遗传疾病患儿风险的夫妇建立不受影响的妊娠。然而，由于误诊的风险，仍建议所有 PGD 患者进行有创性测试。母体血浆中无细胞胎儿 DNA 的发现为非侵入性产前诊断提供了可能性。研究表明，通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）分析联合单等位基因碱基延伸反应（SABER）或大小分离方法，可以从无细胞胎儿 DNA 中检测到胎儿单基因疾病。在此方法中，无细胞胎儿 DNA 比母体 DNA 片段小，基于此可以对其进行富集。最近的研究表明，两种方法的结合提高了检测的准确性。本研究结合了这两种方法，检测了来自 4 例 PGD 妊娠的母体血浆中胎儿父系遗传基因突变。在所有病例中，均正确检测到了突变的存在或缺失。该联合方法可用于由单基因突变引起的疾病的无风险产前诊断，特别是对于那些由于流产风险而选择不进行有创性产前确认的进行 PGD 的夫妇。
