Abstract | OBJECTIVE: To examine the performance of chromosome-selective sequencing of cell-free (cf) DNA in maternal blood for assessment of fetal sex chromosome aneuploidies. METHODS: This was a case-control study of 177 stored maternal plasma samples, obtained before fetal karyotyping at 11-13 weeks of gestation, from 59 singleton pregnancies with fetal sex chromosome aneuploidies (45,X, n = 49; 47,XXX, n = 6; 47,XXY, n = 1; 47,XYY, n = 3) and 118 with euploid fetuses (46,XY, n = 59; 46,XX, n = 59). Digital analysis of selected regions (DANSR™) on chromosomes 21, 18, 13, X and Y was performed and the fetal-fraction optimized risk of trisomy evaluation (FORTE™) algorithm was used to estimate the risk for non-disomic genotypes. Performance was calculated at a risk cut-off of 1:100. RESULTS: Analysis of cfDNA provided risk scores for 172 (97.2%) samples; 4 samples (45,X, n = 2; 46,XY, n = 1; 46,XX, n = 1) had an insufficient fetal cfDNA fraction for reliable testing and 1 case ( 47,XXX) failed laboratory quality control metrics. The classification was correct in 43 (91.5%) of 47 cases of 45,X, all 5 of 47,XXX, 1 of 47,XXY and 3 of 47,XYY. There were no false-positive results for monosomy X. DISCUSSION: Analysis of cfDNA by chromosome-selective sequencing can correctly classify fetal sex chromosome aneuploidy with reasonably high sensitivity.
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Authors | Kypros H Nicolaides, Thomas J Musci, Craig A Struble, Argyro Syngelaki, M M Gil |
Journal | Fetal diagnosis and therapy
(Fetal Diagn Ther)
Vol. 35
Issue 1
Pg. 1-6
( 2014)
ISSN: 1421-9964 [Electronic] Switzerland |
PMID | 24335155
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 S. Karger AG, Basel. |
Topics |
- Aneuploidy
- Case-Control Studies
- Chromosome Disorders
(diagnosis)
- Female
- Humans
- Karyotyping
- Maternal Serum Screening Tests
(methods)
- Pregnancy
- Sensitivity and Specificity
- Sequence Analysis, DNA
- Sex Chromosomes
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