Maternal plasma mRNA species in fetal heart defects: a potential for molecular screening

Prenat Diagn. 2016 Aug;36(8):738-43. doi: 10.1002/pd.4853. Epub 2016 Jul 4.

Abstract

Objective: To verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy.

Methods: NanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated.

Results: Six genes with differential expression, namely FALZ, PAPP-A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75(th) centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75(th) centile.

Conclusion: These data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening.

MeSH terms

  • Antigens, Nuclear / genetics
  • Case-Control Studies
  • Cell Cycle Proteins / genetics
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / genetics
  • Discriminant Analysis
  • Female
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Linear Models
  • Multivariate Analysis
  • Nerve Tissue Proteins / genetics
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy-Associated Plasma Protein-A / genetics
  • Prenatal Diagnosis
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Messenger / blood*
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Tenascin / genetics
  • Transcription Factors / genetics

Substances

  • Antigens, Nuclear
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • SAV1 protein, human
  • Tenascin
  • Transcription Factors
  • fetal Alzheimer antigen
  • tenascin X
  • STK4 protein, human
  • Protein Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
  • PRKACB protein, human
  • Pregnancy-Associated Plasma Protein-A
  • PAPPA protein, human