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| Application of whole exome sequencing in prenatal diagnosis of fetuses with congenital talipes equinovarus |
| The Third Affiliated Hospital of Zhengzhou University，Zhengzhou, Henan Province, 450000 |
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Abstract To explore the value of whole exome sequencing (WES) technology in the prenatal diagnosis of fetuses with congenital talipes equinovarus (CTEV). Methods：The single fetuses with CTEV evaluated by prenatal ultrasonography and with normal chromosomes by G-band karyotype analysis and chromosome microarray analysis (CMA) were included as the research subjects. After obtaining informed consent from the mothers and other family members, WES technology was used to analyze these fetuses. After the variants of the fetuses were classified according to the interpretation guideline of the genetic variation by American College of Medical Genetics and Genomics (ACMG), the detection rates of pathogenic or likely pathogenic genes of WES were compared among the fetuses with different types of CTEV. The correlation between the CTEV of the fetuses and their single gene variants was analyzed. Results: 12 fetuses (31.6%, 12/38) were found to carry pathogenic or likely pathogenic genes in 38 fetuses with CTEV. The WES detection rate of the fetuses with complex type CTEV was 40% (12 cases, 12/30), which of the fetuses with isolated type CTEV was 0% (0 case, 0/8), which of the fetuses with bilateral type was 33.3% (9 cases, 9/27), and which of the fetuses with unilateral type CTEV was 27.3% (3 cases, 3/11). There was significant difference in the WES detection rate between the fetuses with complex type CTEV and the fetuses with isolated type CTEV (P=0.039). 15 pathogenic or likely pathogenic monogenic variants of the fetuses were identified, which including PEX1 (NM_000466.3c.892_895dupp.N299Ifs*2), SMAD3 (NM_005902.4:c.730G >A: p.V244I), CRTAP (NM_006371.5: c. 634C >T: p.R212*) ZC4H2 (NM_018684.4: c.332T >C: (p.L111P), TGFBR1 (NM_004612.4: c.1012A >G: p.N338D), FKBP10 and (NM_021939.4: c.1490G >A: (p.W497*). The variant of FKBP10 (NM_021939.4: c.831dup: (p.G278Rfs*95) of the fetuses with CTEV was the new pathogenic variants reported for the first time in this study. Conclusion: WES is effective for prenatal diagnosing the fetuses with CTEV. It is recommended to perform WES for the fetuses with the complex CTEV and normal chromosome detection.
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