Purpose: Current diagnostic methods for chromosomal abnormalities rely mainly on karyotyping and occasionally fluorescent in situ hybridization or quantitative polymerase chain reaction. We describe an alternative molecular method for the detection of trisomy 21 involving mass spectrometric analysis of single nucleotide polymorphisms.
Methods: In collaboration with Sequenom, Inc., 350 blinded amniotic fluid, amniocyte culture, chorionic villus, or amniotic fluid supernatant samples were analyzed for trisomy 21 using SNP analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Peak ratios were calculated for heterozygous genotypes and compared to control values generated from known euploid samples. An analytical algorithm using standard deviations from control values was used to determine the probability of a sample being affected or unaffected.
Results: Seventy-three trisomy 21 samples from among the 350 blinded samples were correctly identified. There were no false-positive or false-negative results among the complete trisomy 21 samples. One sample exhibiting mosaicism for trisomy 21 was identified as being unaffected.
Conclusions: MALDI-TOF mass spectrometry is a robust and reproducible method for the detection of trisomy 21. Its amenability to high-throughput analysis and high degree of multiplexing make it a potential future diagnostic tool for the detection of other aneuploidies as well.