CNV-seq联合细胞检测技术对额外小标记染色体的产前诊断和遗传学分析OA

Objective To explore the value and clinical significance of applying molecular and cytogenetic techniques in the prenatal diagnosis of fetuses carrying a small supernumerary marker chromosome(sSMC).Methods A retrospective analysis was conducted on 32 876 pregnant women who underwent prenatal diagnosis at Liuzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children's Medical Center Liuzhou Hospital from January 2018 to December 2024.Prenatal samples,including chorionic villi,amniotic fluid,and umbilical cord blood,were subjected to cell culture and G-banded karyotype analysis.Samples identified with sSMC were further analyzed using copy number variation sequencing(CNV-seq)to determine their chromosomal origin and pathogenicity.When necessary,C-banding and N-banding techniques were used to further characterize the composition of the sSMC.Results Among the 32 876 prenatal diagnostic samples,35 fetuses with sSMC karyotypes were identified,with an overall detection rate of 1.1‰.Of these,21 cases(60%,21/35)were non-mosaic sSMC,and 14 cases(40%,14/35)were mosaic sSMC.CNV-seq analysis of the 35 fetuses revealed pathogenic copy number variations in 16 cases,involving chromosomes 1,4,9,10,11,12,15,18,22,X,and Y.Among these cases,only one pregnancy resulted in a full-term live birth,while the remaining 15 pregnancies were terminated.Among the 19 cases with non-pathogenic sSMC,two pregnancies were terminated,one resulted in stillbirth,and 16 continued to full-term delivery.Follow-up by telephone revealed no abnormalities in these infants.Conclusion The combination of cytogenetic and molecular genetic techniques enables accurate determination of the size and origin of sSMCs and facilitates the assessment of their pathogenicity.This approach provides an important theoretical basis for the prenatal diagnosis and genetic counseling of fetuses carrying sSMCs.