Anti-GATA5 (aa 336-397) polyclonal antibody

BackgroundBicuspid aortic valve (BAV) is the most common congenital heart defect with a prevalence of 1%-2% in the general population. NOTCH1, SMAD6, and GATA5 are associated with BAV in humans, but few cases have been reported that did not involve NOTCH1. Here, we identified novel in-frame variants in SMAD6 (c.1168_1173dup; p.Gly390_Ile391dup) in a BAV patient, who presented with dilatation of the ascending aorta and severe calcification of the aortic valve. MethodsTwenty BAV associated genes were screened by exome sequencing. Functional effects of SMAD6 variant were investigated using bone morphogenetic protein (BMP) signaling assays through in vitro functional study. ResultsExome sequencing revealed he had novel in-frame variants in the SMAD6 gene (c.1168_1173dup; p.Gly390_Ile391dup). SMAD6 is known to be an inhibitory protein in the BMP signaling pathway. In vitro functional study of the p.Gly390_Ile391dup variant revealed impaired inhibition of BMP signaling and BMP-induced alkaline phosphatase activity. ConclusionIn conclusion, we identified a novel SMAD6 variant causing a severely calcified BAV and TAA, which contributes to our understanding of the clinical and genetic background of SMAD6-related BAV.

BackgroundCongenital diaphragmatic hernia (CDH) is characterized by a defective closure of the diaphragm occurring as an isolated defect in 60% of cases. Lung size, liver herniation, and pulmonary circulation are major prognostic indices. Isolated CDH genetics is heterogeneous and poorly understood. Whether genetic lesions are also outcome determinants has never been explored. ObjectivesTo identify isolated CDH genetic causes, to fine map the mutational burden, and to search for a correlation between the genotype and the disease severity and outcome. MethodsTargeted massively parallel sequencing of 143 human and mouse CDH causative and candidate genes in a cohort of 120 fetuses with isolated CDH and detailed outcome measures. ResultsPathogenic and likely pathogenic variants were identified in 10% of the cohort. These variants affect both known CDH causative genes, namely, ZFPM2, GATA4, and NR2F2, and new genes, namely, TBX1, TBX5, GATA5, and PBX1. In addition, mutation burden analysis identified LBR, CTBP2, NSD1, MMP14, MYOD1, and EYA1 as candidate genes with enrichment in rare but predicted deleterious variants. No obvious correlation between the genotype and the phenotype or short-term outcome has been found. ConclusionTargeted resequencing identifies a genetic cause in 10% of isolated CDH and identifies new candidate genes.