title: Maternal plasma mRNA species in fetal heart defects: a potential for molecular screening.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine and Surgery, Division of Obstetrics and Prenatal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Curti
authors.affiliation: Geneticlab, Noventa Vicentina, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lapucci
authors.affiliation: Geneticlab, Noventa Vicentina, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Berto
authors.affiliation: Pediatric Cardiology and Adult Congenital Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Prandstraller
authors.affiliation: Department of Medicine and Surgery, Division of Obstetrics and Prenatal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Perolo
authors.affiliation: Department of Medicine and Surgery, Division of Obstetrics and Prenatal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Rizzo
authors.affiliation: Department of Medicine and Surgery, Division of Obstetrics and Prenatal Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Farina
mesh_terms: D034961:Antigens, Nuclear / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000235:genetics; D016002:Discriminant Analysis; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016014:Linear Models; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000235:genetics; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics; D011296:Prenatal Diagnosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D019063:Tenascin / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000092468:Bromodomain Containing Proteins; D000099317:Hippo Kinases
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011266:Pregnancy-Associated Plasma Protein-A; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D019063:Tenascin; D014157:Transcription Factors; C415864:SAV1 protein, human; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins; C081865:tenascin X; C095566:STK4 protein, human; D000099317:Hippo Kinases; C517760:PRKACB protein, human; C579283:PAPPA protein, human