Abstract To explore the application value of single nucleotide polymorphism array (SNP array) in the genetic etiology of fetal foot varus. Methods: The chromosome karyotype analysis and chromosome microarray detection of 166 fetuses with foot varus during the second and third trimester of pregnancy through amniotic fluid or umbilical cord blood samples were analyzed retrospectively. The Illumina Human Cyto 12 microarray chip was used to detect copy number variations (CNVs) of the whole genome. The pathogenicity of CNVs was analyzed combined with the review of the international CNVs database, the database of genomic variants (DGV) and the PubMed literature database. Results: In the 166 fetuses, there were 13 cases with chromosome karyotype abnormality with 7.8% (13/166) of the detection rate, and which included 6 cases of 18-trisomy syndrome, 2 cases of 21-trisomy syndrome, and 1 case of Klinefelter syndrome, 1 case of superandrogenic syndrome, 1 case involving 18-trisomy syndrome combined with Klinefelter syndrome, 1 case of chromosome deletion, 1 case of derived chromosomes. SNP array had detected 24 cases of abnormalities. The detection rate was 14.4% (24/166), which was significant higher than that of chromosome karyotype abnormality. Of the 18 cases with pathogenicity, the results of 13 cases by SNP array detection were consistent with the results by karyotype analysis, and 5 cases with microdeletion/microduplication syndrome detected by SNP array were not found by karyotype analysis. Conclusion: SNP array for detecting fetuses with foot varus during the second and third trimesters of pregnancy helps to find abnormalities of the chromosomal submicroscopic structure that cannot be found by karyotype analysis, and can improve the diagnosis of the genetic etiology of fetal foot varus.
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