Marfan syndrome is an autosomal dominant connective tissue disorder, and mutations in the FBN1 and TGFBR2 genes have been identified in probands with MFS and related phenotypes. Using DHPLC and sequencing, we studied the mutation spectrum in 65 probands with Marfan syndrome and related phenotypes. A total of 24 mutations in FBN1 were identified, of which 19 (nine missense, six frameshift, two nonsense and two affecting splice junctions) were novel. In the remaining 41 probands, six were identified to have novel TGFBR2 mutations (one frameshift and five missense mutations). All novel mutations found in this study were confirmed to be absent in 50 unrelated normal individuals of the same ethnic background. In probands who fulfilled the Ghent criteria (n = 16), mutations in FBN1 were found in 81% of cases. None of those with TGFBR2 mutations fulfilled the Ghent criteria. Novel missense mutations of unknown significance were classified according to the latest ACMG guidelines and their likelihood to be causative was evaluated.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ajmg.a.32918 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A divergent two-domain structure of the anti-Müllerian hormone prodomain.
Proc Natl Acad Sci U S A
January 2025
Department of Molecular & Cellular Biosciences, University of Cincinnati, Cincinnati, OH 45267.
TGFβ family ligands are synthesized as precursors consisting of an N-terminal prodomain and C-terminal growth factor (GF) signaling domain. After proteolytic processing, the prodomain typically remains noncovalently associated with the GF, sometimes forming a high-affinity latent procomplex that requires activation. For the TGFβ family ligand anti-Müllerian hormone (AMH), the prodomain maintains a high-affinity interaction with its GF that does not render it latent.
View Article and Find Full Text PDFPIEZO1 attenuates Marfan syndrome aneurysm development through TGF-β signaling pathway inhibition via TGFBR2.
Eur Heart J
November 2024
Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Article Synopsis
- * The study explored the role of PIEZO1, a mechanosensitive ion channel, in MFS, revealing that its activation could potentially offer a new therapeutic approach against TAA.
- * Results showed that knocking out PIEZO1 in mice worsened TAA and activated harmful pathways, while pharmacological activation of PIEZO1 helped prevent these negative effects, highlighting its potential as a target for new MFS treatments.
Exploring the potential of TGFβ as a diagnostic marker and therapeutic target against cancer.
Biochem Pharmacol
January 2025
Departments of Medical Oncology & Therapeutics Research, USA. Electronic address:
Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine that exerts its biological effects through a complex process of activation and signaling. Initially synthesized in an inactive form bound to latency-associated peptide (LAP), TGF-β requires release from the extracellular matrix via proteolytic cleavage or integrin-mediated activation to engage with its receptors. Once active, TGF-β binds to type II receptor (TβRII), which then phosphorylates and activates type I receptor (TβRI), triggering downstream signaling cascades, including both Smad-dependent and non-Smad pathways.
View Article and Find Full Text PDFDifferential Analysis of Pathogenic Variants in Thoracic Aortic Aneurysm and Dissection at Different Ages.
Genet Test Mol Biomarkers
November 2024
Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children, Capital Medical University; Center of Rare Diseases, National Center for Children's Health; Beijing Children's Hospital, Capital Medical University, Beijing, China.
To identify genetic variants associated with Stanford A thoracic aortic aneurysm and dissection (ATAAD) using whole-exome sequencing (WES) and analyze positive mutation rates among patients of different onset ages. WES was performed on 62 sporadic Chinese ATAAD patients (51-74 years old), and then grouped based on onset age together with 73 previously reported TAAD patients (19-50 years old): ≤35, 36-45, 46-55, and >55 years. The proportion of patients with pathogenic/likely pathogenic (P/LP) variants in TAAD causal genes was compared across groups.
View Article and Find Full Text PDFDiscovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology.
Proc Natl Acad Sci U S A
November 2024
Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030.
Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!