Noninvasive prenatal detection of fetal sex chromosome abnormalities using the semiconductor sequencing platform (SSP) in Southern China

Jiexia Yang,Yi Li,Haishan Peng,Fangfang Guo,Haoxin Oy,Aihua Yin,Jian Lu,Dongmei Wang,Yixia Wang,Yaping Hou

doi:10.1007/s10815-020-02056-2

Abstract

BackgroundNoninvasive prenatal testing (NIPT) has been widely used to screen for fetal aneuploidies, including fetal sex chromosome aneuploidies (SCAs). However, there is less information on the performance of NIPT in detecting SCAs.MethodsA cohort of 47,800 pregnancies was recruited to review the high-risk NIPT results for SCAs. Cell-free fetal DNA (cffDNA) was extracted and sequenced. All NIPT high-risk cases were recommended to undergo invasive prenatal diagnosis for karyotyping analysis and chromosome microarray analysis (CMA).ResultsA total of 238 high-risk cases were detected by NIPT, including 137 cases of 45,X, 27 cases of 47,XXX, and 74 cases of 47,XYY/47,XXY. Prenatal diagnosis, including karyotyping analysis and CMA, was available in 170 cases. The positive predictive value (PPV) was 30.00% for 45,X, 70.58% for 47,XXX, and 81.13% for 47,XYY/47,XXY. In addition, 13 cases of sex chromosome mosaicism and 9 cases of sex chromosome CNVs were incidentally found in this study.ConclusionOur study showed that NIPT was reliable for screening SCAs based on a large sample, and it performed better in predicting sex chromosome trisomies than monosomy X. Our study will provide an important reference for clinical genetic counseling and further processing of the results.

Highlights

Sex chromosome aneuploidies (SCAs) are numeric abnormalities of sex chromosomes that are relatively common genetic conditions, affecting as many as 1/400 newborns, approximately twice as frequent in newborns as trisomy 21 [1]
The majority (80.8%) of pregnant women were at 12–24 gestational age when Noninvasive prenatal testing (NIPT) was performed, and 29.03% were at high risk for serological screening
Sexual chromosomal abnormalities detected by NIPT were caused by changes in the ratio of fetal X to Y chromosomes, which was reported in a previous study [19]

Summary

Introduction

Sex chromosome aneuploidies (SCAs) are numeric abnormalities of sex chromosomes that are relatively common genetic conditions, affecting as many as 1/400 newborns, approximately twice as frequent in newborns as trisomy 21 [1]. The most common SCA karyotypes include 45,X (Turner syndrome), 47,XXY, 47,XXX (Triple X syndrome), 47,XYY syndrome, and sex chromosome mosaicism. Noninvasive prenatal testing (NIPT) has been widely used to screen pregnant women for fetal aneuploidies, including fetal SCAs [5, 6]. NIPT has become a first-tier screening for aneuploidies in low- and high-risk populations, and there will likely be a significant increase in the incidence of positive screening results for SCAs [7]. Noninvasive prenatal testing (NIPT) has been widely used to screen for fetal aneuploidies, including fetal sex chromosome aneuploidies (SCAs). All NIPT high-risk cases were recommended to undergo invasive prenatal diagnosis for karyotyping analysis and chromosome microarray analysis (CMA). Results A total of 238 high-risk cases were detected by NIPT, including 137 cases of 45,X, 27 cases of 47,XXX, and 74 cases of 47,XYY/47,XXY. 13 cases of sex chromosome mosaicism and 9 cases of sex chromosome CNVs were incidentally found in this study

Methods

Results

Discussion

Conclusion