Li Ying, Page-Christiaens Godelieve C M L, Gille Johan J P, Holzgreve Wolfgang, Hahn Sinuhe
Department of Research, University Women's Hospital, University of Basel, Basel, Switzerland.
Prenat Diagn. 2007 Jan;27(1):11-7. doi: 10.1002/pd.1608.
Achondroplasia is the most common form of short-limbed dwarfism in humans and is caused by mutations in the FGFR3 gene. Currently, prenatal diagnosis of this disorder relies on invasive procedures. Recent studies have shown that fetal single gene point mutations could be detected in cell-free DNA (cf-DNA) from maternal plasma by either the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single allele base extension reaction (SABER) approach or the size fractionation of cf-DNA in maternal plasma. Here, we combined the two approaches to non-invasively examine the fetal G1138A mutation in maternal plasma. cf-DNA was extracted from maternal plasma samples obtained from two pregnant women at risk for achondroplasia. The fetal G1138A mutation was determined by the analysis of size-fractionated cf-DNA in maternal plasma using MALDI-TOF MS with SABER approach and homogenous MassEXTEND (hME) assay, respectively. The fetal G1138A mutation was detectable in the two achondroplasia-affected pregnancies by the analysis of cf-DNA in maternal plasma using MALDI-TOF MS. However, the size-fractionation approach led to a more precise detection of the fetal mutation in both analyses. This analysis would be suitable for non-invasive prenatal diagnosis of diseases caused by fetal single gene point mutations.
软骨发育不全是人类短肢侏儒症最常见的形式，由FGFR3基因突变引起。目前，这种疾病的产前诊断依赖于侵入性操作。最近的研究表明，通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）检测结合单等位基因碱基延伸反应（SABER）方法，或通过对母血中游离DNA（cf-DNA）进行大小分级，可以检测出胎儿的单基因点突变。在此，我们结合这两种方法对母血中的胎儿G1138A突变进行非侵入性检测。从两名有软骨发育不全风险的孕妇的母血样本中提取cf-DNA。分别使用MALDI-TOF MS结合SABER方法和均相MassEXTEND（hME）检测法，通过分析母血中大小分级的cf-DNA来确定胎儿的G1138A突变。使用MALDI-TOF MS分析母血中的cf-DNA，在这两例受软骨发育不全影响妊娠中均可检测到胎儿的G1138A突变。然而，在这两种分析中，大小分级方法对胎儿突变的检测更为精确。该分析适用于胎儿单基因点突变所致疾病的非侵入性产前诊断。
