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Noninvasive genotyping fetal Kell blood group ( KEL1 ) using cell‐free fetal DNA in maternal plasma by MALDI‐TOF mass spectrometry
Author(s) -
Li Ying,
Finning Kirstin,
Daniels Geoff,
Hahn Sinuhe,
Zhong Xiaoyan,
Holzgreve Wolfgang
Publication year - 2008
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.1936
Subject(s) - fetus , cell free fetal dna , genotyping , cord blood , medicine , prenatal diagnosis , typing , serology , gestation , genotype , andrology , obstetrics , pregnancy , immunology , biology , antibody , gene , genetics
Background Alloimmunization against the fetal Kell ( KEL1 ) blood group antigen is gaining importance relative to the Rhesus problem and is the second most important cause of hemolytic disease of the fetus and newborn. Molecular diagnosis for fetal KEL1 , which currently involves invasive procedures, is routinely done for accessing whether a fetus is at risk. Here we developed a matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS)‐based single allele‐based extension reaction (SABER) to examine the fetal KEL1 gene from KEL1 ‐negative pregnant women using cell‐free fetal DNA in maternal plasma. Methods Thirty‐two maternal plasma samples taken at the second and third trimesters of gestation (median: 21.5 weeks) were examined with MALDI‐TOF MS‐based SABER. The results were confirmed by serological tests on cord blood or polymerase chain reaction (PCR) typing on amniocyte‐derived fetal DNA. Results We were able to detect the fetal KEL1 allele in 11 of the 13 KEL1 ‐positive samples. No false positive results were scored. The paternal KEL1 allele could be correctly determined in 94% of cases (30/32). Conclusions Our results indicated that the MALDI‐TOF MS‐based SABER has been used successfully for the detection of the fetal KEL1 status with the accuracy of 94%. Further, large‐scale study, such as multicenter study, can now be explored for clinical application. Copyright © 2008 John Wiley & Sons, Ltd.