Non-invasive prenatal testing of trisomy 18 by an epigenetic marker in first trimester maternal plasma.
BACKGROUND
Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.


RESULTS
A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.


CONCLUSIONS
Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.
Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea.
Da Eun
DE
Lee
Shin Young
SY
Kim
Ji Hyae
JH
Lim
So Yeon
SY
Park
Hyun Mee
HM
Ryu
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005333:Fetus; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D015843:Serpins / Q000097:blood / Q000235:genetics*; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics*; D000073842:Trisomy 18 Syndrome
D005819:Genetic Markers; C085344:SERPIN-B5; D015843:Serpins