Rabbit Anti-Human SERPINC1 Polyclonal antibody

Objective The molecular basis for the antithrombin (AT) deficiency and dilated cardiomyopathy (DCM) combined in a Japanese patient was investigated. Methods We analyzed candidate genes - SERPINC1 for AT deficiency, and TNNT2 and LMNA for DCM. In addition, we examined the characteristics of recombinant mutant AT and evaluated the LMNA mutation associated with DCM by molecular modeling. Results Genome sequencing of SERPINC1 revealed a C-to-A transversion in exon 6 that resulted in a p.Pro439Thr mutation of AT, which was previously reported as a pleiotropic effect type II AT deficiency (AT Budapest5). However, expression experiments with recombinant 439Thr-AT showed normal heparin affinity, slightly reduced secretion, and low specific activity, which suggested that this mutation exhibits an intermediate feature of type I and type II AT deficiencies. In a survey of gene abnormalities causing DCM, we found no causative gene defect in TNNT2; however, we identified a G-to-C transversion in LMNA that resulted in a novel p.Asp357His mutation in lamin A/C. This acidic-to-basic residue substitution might have impaired the head-to-tail association of two lamin dimers leading to DCM. Further, we identified both SERPINC1 and LMNA mutations in the patient's daughter and son, both of whom had AT deficiency. These data suggested that a p. Pro439Thr mutation in SERPINC1 and a p. Asp357His mutation in LMNA might have cosegregated in this family, associated with AT deficiency and DCM, respectively. Conclusions We identified missense mutations in SERPINC1 and LMNA genes to be associated with AT deficiency and DCM, respectively, which might have cosegregated in the family of the patient.

The current study aimed to elucidate the molecular mechanisms and identify the potential key genes and pathways for metastatic uveal melanoma (UM) using bioinformatics analysis. Gene expression microarray data from GSE39717 included 39 primary UM tissue samples and 2 metastatic UM tissue samples. Differentially expressed genes (DEGs) were generated using Gene Expression Omnibus 2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. The web-based STRING tool was adopted to construct a protein--protein interaction (PPI) network. The MCODE tool in Cytoscape was used to generate significant modules of the PPI network. A total of 213 DEGs were identified. GO and KEGG analyses revealed that the upregulated genes were mainly enriched in extracellular matrix organization and blood coagulation cascades, while the downregulated DEGs were mainly related to protein binding, negative regulation of ERK cascade, nucleus and chromatin modification, and lung and renal cell carcinoma. The most significant module was extracted from the PPI network. GO and KEGG enrichment analyses of the module revealed that the genes were mainly enriched in the extracellular region and space organization, blood coagulation process, and PI3K-Akt signaling pathway. Hub genes, including FN1, APOB, F2, SERPINC1, SERPINA1, APOA1, FGG, PROC, ITIH2, VCAN, TFPI, CXCL8, CDH2, and HP, were identified from DEGs. Survival analysis and hierarchical clustering results revealed that most of the hub genes were associated with prognosis and clinical progression. Results of this bioinformatics analysis may provide predictive biomarkers and potential candidate therapeutic targets for individuals with metastatic UM.