MALDI-TOF MS in Prenatal Genomics

Abstract

Prenatal diagnosis aims either to provide the reassurance to the couples at risk of having an affected child by timely appropriate therapy or to give the parents a chance to decide the fate of the unborn babies with health problems. Invasive prenatal diagnosis (IPD) is accurate, however, carrying a risk of miscarriage. Noninvasive prenatal diagnosis (NIPD) has been developed based on the existing of fetal genetic materials in maternal circulation; however, a minority fetal DNA in majority maternal background DNA hinders the detections of fetal traits. Different protocols and assays, such as homogenous MassEXTEND (hME), single allele base extension reaction (SABER), precise measuring copy number variation of each allele, and quantitative methylation and expression analysis using the high-throughput sensitive matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), allow NIPD for single gene disorders, fetal blood group genotyping and fetal aneuploidies as well as the development of fetal gender-independent biomarkers in maternal circulation for management of pathological pregnancies. In this review, we summarise the use of MALDI-TOF MS in prenatal genomics.

Diagnostic accuracy of noninvasive polymerase chain reaction testing for the determination of fetal rhesus C, c and E status in early pregnancy

“…[31][32][33] Recently, Li et al reported that use of a MALDI-TOF MS single allele-based extension reaction for detection of KEL-1 resulted in an accuracy of 94%. 32 However, more MALDI-TOF MS studies are required before this technology can replace real-time PCR in diagnostic laboratories determining fetal blood groups in maternal plasma.…”

Mass spectrometric based analysis, characterization and applications of circulating cell free DNA isolated from human body fluids

“…In addition, methods based on matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry such as homogenous MassEXTEND (hME), single allele base extension reaction (SABER), and the allele-specific base extension reaction (ASBER) have been successfully used to characterize CCFDNA [112–129, Table 2]. The analysis of CCFDNA normally performed using qPCR suffers from sensitivity issues as well as the limited ability to detect gene mutations at preselected positions within a gene.…”

“…MALDI-TOF MS analysis of circulating cell free DNA from maternal plasma or urine has emerged as an important technique for prenatal diagnosis, fetal genotyping and analyzing kidney transplant patients which previously were monitored by conventional invasive procedures like chorionic villus, amniocentesis and blood tests [112]. Similar to the ESI-MS-SOMA method, MALDI-TOF does not act as a stand-alone technique for the analysis of genetic alterations in circulating cell free DNA but incorporates protocols such as homogenous MassEXTEND (hME), single allele base extension reaction (SABER) or the allele-specific base extension reaction (ASBER) assays [Figure 2, Figure 3].…”

Detection of Copy Number Variation by SNP-Allelotyping

“…Thus, this variability of allelic frequency may be used to detect CNVs. Such an approach has been used to diagnose the trisomy of chromosome 21 (Zhong & Holzgreve, 2009), however, it is still unknown whether this approach can be used to detect an abnormal CNV of a DNA segment on a chromosome, such as the CMT1A mutation.…”