Determination of Fetal RHD Genotype Including the RHD Pseudogene in Maternal Plasma

J Clin Lab Anal. 2017 May;31(3):e22052. doi: 10.1002/jcla.22052. Epub 2016 Sep 6.

Abstract

Objective: To examine the accuracy of fetal RHD genotype and RHD pseudogene determination in a multiethnical population.

Methods: Prospective study involving D-negative pregnant women. Cell-free DNA was extracted from 1 ml of maternal plasma by an automated system (MagNA Pure Compact, Roche) and real-time PCR was performed in triplicate targeting the RHD gene exons 5 and 7. Inconclusive samples underwent RHD pseudogene testing by real-time PCR analysis employing novel primers and probe.

Results: A positive result was observed in 128/185 (69.2%) samples and negative in 50 (27.0%). Umbilical cord blood phenotype confirmed all cases with a positive or negative PCR result. Seven (3.8%) cases were found inconclusive (exon 7 amplification only) and RHD pseudogene testing with both conventional and real-time PCR demonstrated a positive result in five of them, while two samples were also RHD pseudogene negative.

Conclusion: Real-time PCR targeting RHD exons 5 and 7 simultaneously in maternal plasma is an accurate method for the diagnosis of fetal D genotype in our population. The RHD pseudogene real-time PCR assay is feasible and is particularly useful in populations with a high prevalence of this allele.

Keywords: DNA/analysis; RhD Blood group system; genotyping techniques; prenatal diagnosis/methods; sensitivity and specificity.

MeSH terms

  • Adult
  • DNA / blood
  • DNA / chemistry
  • DNA / genetics
  • Female
  • Genotyping Techniques / methods*
  • Humans
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Prospective Studies
  • Pseudogenes / genetics*
  • Rh-Hr Blood-Group System / genetics*
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Rh-Hr Blood-Group System
  • DNA