Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population

Abstract

Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.

Microduplication and Microdeletion Syndromes Diagnosed Prenatally Using Single Nucleotide Polymorphism Array

“…A high-risk result must be confirmed. In one study, from six high-risk results, only one was confirmed with a diagnostic of microdeletion [ 16 ].…”

Approach and Management of Pregnancies with Risk Identified by Non-Invasive Prenatal Testing

“…The ongoing study is the second one conducted in Romania, focusing on a case load of 1400 cases. It follows the previous survey [3], which presented the genetic counseling and management of 380 cases. The current study compares NIPT high-risk cases with confirmed positive cases.…”

“…Public databases (DECIPHER, OMIM, NCBI) were utilized for data interpretation. Statistical analysis was performed as described earlier [3].…”

“…In 2014, the first cases in Romania underwent testing, and the preliminary findings were previously published [3]. Initially, NIPT was used to detect common fetal aneuploidies [4] and later expanded to include screening for rare fetal aneuploidies, incorporating a growing repertoire of 92 chromosomal number variations (CNVs).…”

A Rare Case of Mosaic 3pter and 5pter Deletion-Duplication with Autism Spectrum Disorder and Dyskinesia

“…An approach of combining complementary classical genetic tests has been used even earlier to resolve rare cytogenetic findings [ 30 ]. The geneticist would discuss options for a noninvasive NIFTY-pro test which enables the identification of 6 autosomal aneuploidies (chromosomes 13, 18, 21, 9, 16, and 22), sex chromosomes aneuploidies, and 84 microdeletion syndromes [ 31 ], or invasive tests of amniotic fluid or chorionic villus for culture and subsequent karyotyping, combined with FISH and microarray analysis to render reproductive counselling for future pregnancies of the parents.…”