Application of Copy Number Variation Sequencing in Prenatal Diagnosis of Fetuses with Nasal Bone Developmental Abnormalities

Objective: To investigate the clinical diagnostic value of copy number variation sequencing (CNV-seq) in fetuses with abnormal nasal bone development suggested by prenatal ultrasound, and to statistically analyze the pathogenic copy number variants (CNVs) additionally detected by this technology compared with traditional karyotype analysis, providing an evidence-based reference for clinical prenatal genetic counseling. Methods: A retrospective cohort study was conducted. Clinical data from 155 pregnant women who underwent invasive prenatal diagnosis at Guigang Maternal and Child Health Hospital from June 2020 to September 2026 due to prenatal ultrasound detection of fetal nasal bone absence or hypoplasia were collected. All study subjects underwent simultaneous chromosome G-banding karyotype analysis and CNV-seq testing. Based on whether ultrasound imaging revealed other associated fetal abnormal signs, the study cases were divided into an isolated nasal bone developmental abnormality group and a non-isolated nasal bone developmental abnormality group. The detection rates of chromosomal genetic abnormalities between the two groups were compared, the additional positive detection performance of CNV-seq relative to karyotype analysis was statistically evaluated, and pregnancy outcome follow-up was completed for 35 cases (33 terminations and 2 live births); outcomes for the remaining 119 cases were incomplete due to loss to follow-up or ongoing pregnancy at the time of data cutoff. Results: Among 155 enrolled cases, 154 cases had complete clinical and laboratory data. Chromosome karyotype analysis detected 30 cases of chromosomal number abnormalities, with an abnormal detection rate of 19.5% (30/154), including 23 cases of trisomy 21, 6 cases of trisomy 18, and 1 case of trisomy 13. In research samples with normal karyotype results, CNV-seq additionally detected a total of 5 pathogenic/likely pathogenic CNVs, accounting for 3.25% (5/154) of all evaluable cases and 4.03% (5/124) of karyotype-normal samples; the involved variant segments included del(6)(p21.2p21.1), del(16)(p12.2p12.2), dup(17)(p13.3), del(15)(q11.2q11.2), and del(22)(q11.2q11.2). The isolated nasal bone developmental abnormality group comprised 86 cases, with 5 genetic abnormalities detected, yielding a detection rate of 5.81%; the non-isolated nasal bone developmental abnormality group comprised 68 cases, with 30 genetic abnormalities detected, yielding a detection rate of 44.12%; the difference in abnormal detection rates between the two groups was statistically significant