Objective
To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD).
Methods
From 2013 to 2019, we performed CMA on 43 fetuses with CVD, who were divided into cerebellar vermis hypoplasia (CVH) group and Dandy‐Walker malformation (DWM) group according to morphological subtypes. Subsequently, WES was performed on 19 fetuses with normal CMA results to identify diagnostic genetic variants (DGVs).
Results
Chromosome aneuploidies and clinically significant copy number variants were identified in 23.3% (10/43) of fetuses, and a significantly higher positive rate was found in fetuses with multiple compared with isolated malformations (36% vs 5.6%, P = .028). STAG2 genes related to Xq25 duplication syndrome was possibly a novel candidate gene for CVD. WES detected eight DGVs in seven genes among the 19 fetuses tested. Autosomal recessive ciliopathies (4/8) caused by TMEM231, CSPP1, and CEP290 mutations, were the most frequent monogenetic diseases, followed by Opitz GBBB syndrome (2/8) caused by MID1 and SPECC1L variants.
Conclusion
The combined use of CMA and WES has the potential to provide genetic diagnoses in 42% (18/43) of fetal CVD. WES should be offered when CMA results are normal.
Growth factor receptor bound protein 7 (GRB7) plays an important role in regulating the growth and metastasis of ovarian cancer. Angiogenesis is the basis for the growth, invasion, and metastasis of malignant tumors. In the current study, we aimed to determine whether GRB7 plays a role in regulating angiogenesis in ovarian cancer. Immunohistochemistry on tissue microarray showed that GRB7 and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) protein expression were positively correlated in ovarian cancer tissues.
GRB7
knockdown suppressed vascular endothelial growth factor A (VEGFA) expression and reduced VEGFA secretion. The effects of
GRB7
-silenced SKOV-3 cells on human umbilical vein endothelial cells (HUVECs) were evaluated using a transwell cell co-culture model, which showed that knockdown of
GRB7
in SKOV-3 cells suppressed HUVEC proliferation, migration, invasion, and tube formation. Moreover, knockdown of
GRB7
in SKOV-3 cells downregulated the expression of proteins associated with angiogenesis, including vascular endothelial growth factor receptor-2 (VEGFR2), mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), extracellular signal-regulated kinases 1 and 2 (ERK1/2), notch receptor 1 (NOTCH1), and delta-like canonical Notch ligand 4 (DLL4) in HUVECs. In conclusion, knockdown of
GRB7
in ovarian cancer cells is an attractive potential therapeutic target for the suppression of angiogenesis in ovarian cancer. GRB7 may regulate angiogenesis through VEGFA/VEGFR2 signaling and its downstream pathways.
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