Maternal mosaicism of sex chromosome causes discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing

Abstract

Objective: To investigate the clinical efficiency of noninvasive prenatal test (NIPT) identifying fetal chromosomal aneuploidies.

Materials and methods: In the present study, 917 women with high-risk pregnancies were invited to participate in an NIPT trial based on an Illumina HiSeq massively parallel sequencing platform. Abnormal cases in NIPT were validated by karyotyping and fluorescence in situ hybridization (FISH) analysis. All of the participants' infants were examined clinically and followed up for at least 6 months.

Results: A total of 35 (3.82%) high-risk pregnancies were detected with abnormal results in NIPT, which included 25 cases (2.73%) of trisomy 21 (Tri21), four cases (0.44%) of trisomy 18 (Tri18), four cases (0.44%) of Turner syndrome (45, X), one cases (0.11%) of Klinefelter's syndrome (47, XXY), and one cases (0.11%) with lower X chromosome concentration. Further validation indicated that one case of Tri18 and the case with lower X chromosome concentration were false positive results (0.22%) in NIPT. Furthermore, it was found that the false positive case with lower X chromosome concentration in NIPT was caused by maternal sex chromosomal mosaicism (45, X and 46, XX).

Conclusion: Our findings indicated that maternal mosaicism of sex chromosome could cause discordant sex chromosomal aneuploidies associated with NIPT. We highly recommended that maternal karyotype should be confirmed for the cases with abnormal results in NIPT.

Keywords: chromosomal aneuploidies; confined placental mosaicism; maternal mosaicism; noninvasive prenatal test; prenatal diagnosis.