Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease. ENG and ACVRL1 gene variants account for up to 96% of all cases, while the remaining cases are caused by SMAD4 or GDF2 variants, or by currently undiscovered mutations in coding or non-coding regions. Here, we report a 47-year-old man who presented with duodenal bulb bleeding and chronic anemia. Physical examination also revealed bleeding from the skin and gingiva. His parents were cousins and one brother and one sister died in infancy from anemia and bleeding. Head computed tomography angiography (CTA) revealed a complete fetal posterior cerebral artery located in the left side, and pulmonary CTA showed pulmonary arterial hypertension. The patient was diagnosed with HHT. Peripheral blood was collected for whole-exome sequencing. Sequencing revealed a mutation in the GDF2 gene, which encodes bone morphogenetic protein-9 (BMP-9). The detected variant, c.352A > T(p.Ile118Phe), was predicted to be a neutral polymorphism; however, the patient’s plasma BMP-9 levels were greatly reduced; we predicted that this might be caused by the GDF2 variant and might be involved in the HHT pathogenesis. Further research in cell lines and animal models is needed to verify the correlation between this GDF2 variant and the pathogenesis of HHT.
Background Multiple myeloma (MM) is a malignant proliferative disease of plasma cells, the incidence of which is increasing every year and remains incurable. The enzyme co-activator-associated arginine methyltransferase 1 (CARM1) is highly expressed in a variety of cancers, such as Hodgkin's lymphoma and acute myeloid leukemia, and CARM1 is closely associated with tumor cell proliferation. However, the role of CARM1 in MM has not been elucidated. Methods and results In this study, we found that CARM1 is overexpressed in MM and closely associated with poor prognosis in MM. CCK-8 and colony formation assays showed that the proliferation of MM cell lines was downregulated when CARM1 expression was knockdown by specific shRNA. Knockdown of CARM1 reduced the proportion of MM cell lines in the S phase and increased the proportion in G0/G1 phase. RNA-seq analysis of the CARM1-KD cell line revealed that it was closely associated with apoptosis and activated the p53 pathway. CCK-8 and apoptosis results showed that CARM1 knockdown made MM cells more sensitive to standard-of-care drugs. Conclusion This study provides an experimental basis for elucidating the pathogenesis of multiple myeloma and searching for potential therapeutic targets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.