Analysis of copy number variation by sequencing in fetuses with nuchal translucency thickening

Copy number variation sequencing (CNV-seq) technique was used to analyze the genetic etiology of fetuses with increased nuchal translucency (NT).

A total of 139 women with gestational 11-14 weeks whose fetuses were detected with increased NT (NT ≥ 2.5 mm) in our hospital from July 2016 to December 2018 were selected. Fetal specimens were performed for karyotyping analysis and CNV sequencing.

According to the nuchal translucency thickness, 2.5-3.4, 3.5-4.4, 4.5-5.4, and more than 5.5 mm, the rates of chromosomal abnormalities were 22.8% (13/57), 30.8% (12/39), 42.1% (8/19), and 62.5% (15/24), respectively. There was significant difference among the incidences of chromosomal abnormalities in four groups (χ²  = 37.69, P < .01) and the incidences increased with fetal NT thickness. Among 139 cases, there were 36 cases (25.9%) with abnormal chromosome karyotypes. Meanwhile, there were 45 cases (32.3%) with abnormal CNV. In the 12 cases with abnormal CNV and normal chromosome karyotypes, there were 2 cases of pathogenic CNV, 7 cases of CNV with unknown clinical significance, and 3 cases of possibly benign CNV. There was no significant difference in CNV between pregnant women in advanced maternal age and those in normal maternal age (χ²  = 1.389, P = .239). In the fetus who showed abnormalities in NT and ultrasonography (χ²  = 5.13, P < .05) and the fetus aborted (χ²  = 113.19, P < .05), the abnormal rate of CNV was higher with statistically significant difference.

CNV-seq combined karyotype analysis should be performed simultaneously in fetuses with increased NT, providing a basis for genetic counseling, which is of great significance for prenatal diagnosis.