title: Noninvasive genotyping fetal Kell blood group (KEL1) using cell-free fetal DNA in maternal plasma by MALDI-TOF mass spectrometry.
abstract: 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.
authors.affiliation: University Women's Hospital/Department of Research, University Hospital, Basel, Switzerland.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Kirstin
authors.initials: K
authors.lastname: Finning
authors.forename: Geoff
authors.initials: G
authors.lastname: Daniels
authors.forename: Sinuhe
authors.initials: S
authors.lastname: Hahn
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhong
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holzgreve
mesh_terms: D004247:DNA / Q000097:blood*; D005260:Female; D005312:Fetal Blood; D005838:Genotype; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics*; D013058:Mass Spectrometry; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D011263:Pregnancy Trimester, Third / Q000097:blood; D012680:Sensitivity and Specificity
chemical_list: D007626:Kell Blood-Group System; D004247:DNA