Identification of circulating placental mRNA in maternal blood of pregnancies affected with fetal congenital heart diseases at the second trimester of pregnancy: implications for early molecular screening.
OBJECTIVE
To investigate whether a significantly aberrant expression of circulating placental mRNA genes related with cardiogenesis can be detected at the second trimester of pregnancy.


METHODS
The study was performed in two stages. First stage (development model group): match of 14 placental tissues at delivery of fetuses with congenital heart disease versus 20 controls. Second stage (validation model group): mRNA amplification of abnormal expressed genes in maternal blood samples from 26 women bearing a fetus with a congenital heart disease matched with 28 controls.


RESULTS
We identified four functional categories of genes possibly involved in abnormal heart development: cardiac morphogenesis: tenascin, thioredoxin, salvador homolog 1 protein; extracellular matrix (ECM) and valvular tissue biosynthesis; placental-associated plasma protein, collagen, type I, alpha 2, fibulin-1, heparanase, procollagen-proline, 2-oxoglutarate 4-dioxygenase, alpha polypeptide II, Jumonji, AT rich interactive domain 1B RBP2-like; normal contractile activity: actinin, alpha 4, fascin homolog 1, actin-bundling protein; and congestive heart failure.


CONCLUSIONS
Altered placental genetic expression was found at term delivery in affected fetuses. The aberration was also confirmed in maternal blood at the second trimester of women bearing a fetus with congenital heart disease. Sensitivity for the most aberrant genes ranged between 42% and 95% at a false positive rate (FPR) of 10%.
Arcelli
Diego
D
Molecular Oncology Lab, Functional Genomics & Bioinformatics unit, Dermopathic Institute of the Immacolata -(IDI) IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy.
Farina
Antonio
A
Cappuzzello
Claudia
C
Bresin
Antonella
A
De Sanctis
Paola
P
Perolo
Antonella
A
Prandstraller
Daniela
D
Valentini
Davide
D
Zucchini
Cinzia
C
Priori
Silvia
S
Rizzo
Nicola
N
D015415:Biomarkers / Q000097:blood; D005260:Female; D005315:Fetal Diseases / Q000097:blood* / Q000235:genetics; D020869:Gene Expression Profiling; D005820:Genetic Testing / Q000379:methods*; D006330:Heart Defects, Congenital / Q000097:blood* / Q000235:genetics; D006801:Humans; D008431:Maternal-Fetal Exchange; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D012333:RNA, Messenger / Q000097:blood*; D012189:Retrospective Studies
D015415:Biomarkers; D012333:RNA, Messenger