Genet Med.: co-auth.: I. Xenarios

Genet Med. 2017 Feb;19(2):169-175. doi: 10.1038/gim.2016.72. Epub 2016 Jun 30.

Cell-free DNA testing of an extended range of chromosomal anomalies: clinical experience with 6,388 consecutive cases.



Cell-free DNA (cfDNA) testing for fetal aneuploidies was broadly implemented for common trisomies and sex-chromosome anomalies (SCAs). However, such an approach identifies only 75 to 85% of clinically relevant aneuploidies.


We present a consecutive series of 6,388 cases, thus uncovering a broader array of aneuploidies, including the rare autosomal trisomies (RATs) and the maternally inherited deletion and duplication copy-number variations (CNVs), with complete and stratified follow-up by amniocentesis. Combined measurements of z-scores and the fetal fraction, in conjunction with fetal cfDNA enrichment, were used to stratify the likelihood of true and false results.


We obtained an incremental diagnostic yield of 50%; RATs and CNVs were found to be significant causes of fetal pathology. Scrutinizing z-scores and the fetal fraction made it possible to distinguish the sources of false-negative results; predict the likelihood of false-positive results for major trisomies and SCAs; classify maternal mosaic SCAs and CNVs, preventing false-positive results; and robustly identify maternally inherited CNVs and detect recurrent genomic disorders as a standardized function of the fetal fraction.


With the clinical pertinence of this broader detection scheme confirmed, we offer recommendations for its implementation.Genet Med 19 2, 169-175.

PMID: 27362910