Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies

被引:3
作者
Basaran, Seher [1 ,2 ]
Has, Recep [3 ]
Kalelioglu, Ibrahim Halil [3 ]
Sivrikoz, Tugba Sarac [3 ]
Karaman, Birsen [1 ,4 ]
Kirgiz, Melike [2 ]
Dehgan, Tahir [2 ]
Kalayci, Tugba [1 ]
Selcuk, Bilge Ozsait [1 ]
Miny, Peter [5 ]
Yuksel, Atil [3 ]
机构
[1] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, TR-34093 Istanbul, Turkey
[2] Ctr Genet Diag & Res PREMED, TR-34394 Istanbul, Turkey
[3] Istanbul Univ, Istanbul Fac Med, Dept Obstet & Gynecol, TR-34093 Istanbul, Turkey
[4] Istanbul Univ, Child Hlth Inst, Dept Pediat Basic Sci, TR-34093 Istanbul, Turkey
[5] Univ Hosp Basel, Inst Med Genet & Pathol, Med Genet, CH-4031 Basel, Switzerland
关键词
cell-free DNA; NIPT; rare chromosomal anomalies; mosaicism; positive predictive values; CONFINED PLACENTAL MOSAICISM; PRENATAL-DIAGNOSIS; FOLLOW-UP; FETAL ANEUPLOIDIES; ABNORMALITIES; CONFIRMATION; TRISOMY;
D O I
10.3390/genes13122389
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The scope of cell-free DNA (cfDNA) testing was expanded to the genome, which allowed screening for rare chromosome anomalies (RCAs). Since the efficiency of the test for RCAs remains below the common aneuploidies, there is a debate on the usage of expanded tests. This study focuses on the confirmatory and follow-up data of cases with positive cfDNA testing for RCAs and cases with screen-negative results in a series of 912 consecutive cases that underwent invasive testing following cfDNA testing. Chorion villus sampling (CVS), amniocentesis (AS), fetal blood sampling, and term placenta samples were investigated using classical cytogenetic and molecular cytogenetic techniques. Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings. This study provides further data to assess the efficiency of expanded cfDNA testing for RATs and SAs. The test efficiency for cfDNA seems to be higher for duplications than for deletions, which is evidence of the role of expert ultrasound in identifying pregnancies at increased risk for chromosome anomalies, even in pregnancies with screen-negatives. Furthermore, we discussed the efficiency of CVS vs. AC in screen-positives for RATs.
引用
收藏
页数:11
相关论文
共 53 条
[51]   Rare chromosome abnormalities, prevalence and prenatal diagnosis rates from population-based congenital anomaly registers in Europe [J].
Wellesley, Diana ;
Dolk, Helen ;
Boyd, Patricia A. ;
Greenlees, Ruth ;
Haeusler, Martin ;
Nelen, Vera ;
Garne, Ester ;
Khoshnood, Babak ;
Doray, Berenice ;
Rissmann, Anke ;
Mullaney, Carmel ;
Calzolari, Elisa ;
Bakker, Marian ;
Salvador, Joaquin ;
Addor, Marie-Claude ;
Draper, Elizabeth ;
Rankin, Judith ;
Tucker, David .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2012, 20 (05) :521-526
[52]   CONFINED PLACENTAL MOSAICISM, IUGR, AND ADVERSE PREGNANCY OUTCOME - A CONTROLLED RETROSPECTIVE UK COLLABORATIVE SURVEY [J].
WOLSTENHOLME, J ;
ROONEY, DE ;
DAVISON, EV .
PRENATAL DIAGNOSIS, 1994, 14 (05) :345-361
[53]   Applying high-throughput sequencing to identify and evaluate foetal chromosomal deletion and duplication [J].
Wu, Yueli ;
Zhang, Linlin ;
Lv, Hong ;
Li, Ying ;
Zhu, Chongyang ;
Tian, Weifang ;
Zhao, Ling .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2020, 24 (17) :9936-9944