NIPT-based prenatal screening of maternal Xq28 copy number variations in a cohort of 80,371 pregnancies

Copy number variation (CNVs) can result in various genomic diseases and variable clinical phenotypes. This study aimed to assess the feasibility and reliability of noninvasive prenatal testing (NIPT) for prenatal screening of maternal copy number variation (CNVs) involving the Xq28 recurrent region.

In this retrospective, single-center study, we analyzed the NIPT data of 80,371 pregnant women to detect the maternal CNVs from 2017 to 2022. Maternal CNVs involving the int22h1/int22h2-mediated chromosome Xq28 recurrent region detected by NIPT were focused on. Chromosomal microarray analysis (CMA) was then performed to validate NIPT results if the remaining maternal lymphocytes were available.

A total of 48 (0.060%, 95% CI 0.045% ~ 0.079%) maternal CNVs involving int22h1/int22h2-mediated chromosome Xq28 recurrent region were identified by NIPT, including 29 (0.036%, 95% CI 0.025% ~ 0.052%) pathogenic deletions sizing from 128.1 kb to 93,244.3 kb, 17 (0.021%, 95% CI 0.013% ~ 0.034%) pathogenic duplications sizing from 442.5 kb to 2059.1 kb and two (0.002%, 95% CI 0.000% ~ 0.009%) variants of uncertain significance (VOUS) sizing from 215.2 kb to 326.1 kb. The detection rates of typical Xq28 recurrent microdeletions and microduplications were 0.005% (4/80,371, 95% CI 0.002% ~ 0.013%) and 0.006% (5/80,371, 95% CI 0.003% ~ 0.015%), respectively. Chromosomal microarray analysis (CMA) was performed to validate NIPT results in 22 cases for which remaining maternal lymphocytes were available. The positive predictive value (PPV) of NIPT for maternal CNV's detection in the 22 cases was 100.0% (95% CI 85.1% ~ 100.0%).

This study illustrated the feasibility and potential of NIPT to detect maternal CNVs involving the Xq28 recurrent region.