Reliable detection of trisomy 21 using MALDI-TOF mass spectrometry.
OBJECTIVE
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.
Huang
Dorothy J
DJ
Laboratory for Prenatal Medicine University Women's Hospital, Department of Research Spitalstrasse 21, CH4031 Basel, Switzerland.
Nelson
Matthew R
MR
Zimmermann
Bernhard
B
Dudarewicz
Lech
L
Wenzel
Friedel
F
Spiegel
Roland
R
Nagy
Balint
B
Holzgreve
Wolfgang
W
Hahn
Sinuhe
S
D000465:Algorithms; D000653:Amniotic Fluid / Q000737:chemistry; D002891:Chromosomes, Human, Pair 21; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*