TY - JOUR
T1 - Cell-free fetal DNA and intact fetal cells in maternal blood circulation
T2 - Implications for first and second trimester non-invasive prenatal diagnosis
AU - Bischoff, Farideh Z.
AU - Sinacori, Mina K.
AU - Dang, Diane D.
AU - Marquez-Do, Deborah
AU - Horne, Cassandra
AU - Lewis, Dorothy E.
AU - Simpson, Jo Leigh
N1 - Funding Information:
These studies were supported by NIH/NICHD contract N01-HD-43203. The authors also thank Audrey Burke for the enrolment of study subjects and specimen collection.
PY - 2002/11
Y1 - 2002/11
N2 - Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.
AB - Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.
KW - Cell-free fetal DNA in maternal plasma
KW - Fetal cells in maternal blood
KW - Fetal chromosomal aneuploidy
KW - Non-invasive prenatal diagnosis
KW - Real-time quantitative PCR
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U2 - 10.1093/humupd/8.6.493
DO - 10.1093/humupd/8.6.493
M3 - Review article
C2 - 12498419
AN - SCOPUS:0036864219
SN - 1355-4786
VL - 8
SP - 493
EP - 500
JO - Human Reproduction Update
JF - Human Reproduction Update
IS - 6
ER -