The Molecular Genetics of Marfan Syndrome

Abstract

Marfan syndrome (MFS) is a complex connective tissue disease that is primarily characterized by cardiovascular, ocular and skeletal systems disorders. Despite its rarity, MFS severely impacts the quality of life of the patients. It has been shown that molecular genetic factors serve critical roles in the pathogenesis of MFS. FBN1 is associated with MFS and the other genes such as FBN2 , transforming growth factor beta (TGF-β) receptors ( TGFBR1 and TGFBR2 ), latent TGF-β-binding protein 2 ( LTBP2 ) and SKI , amongst others also have their associated syndromes, however high overlap may exist between these syndromes and MFS. Abnormalities in the TGF-β signaling pathway also contribute to the development of aneurysms in patients with MFS, although the detailed molecular mechanism remains unclear. Mutant FBN1 protein may cause unstableness in elastic structures, thereby perturbing the TGF-β signaling pathway, which regulates several processes in cells. Additionally, DNA methylation of FBN1 and histone acetylation in an MFS mouse model demonstrated that epigenetic factors play a regulatory role in MFS. The purpose of the present review is to provide an up-to-date understanding of MFS-related genes and relevant assessment technologies, with the aim of laying a foundation for the early diagnosis, consultation and treatment of MFS.

The Fibrillin‐1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells

“…Fibrillin‐1 (FBN1) belongs to the fibrillin family, which includes FBN1, FBN2, and FBN3, and contributes to the diagnosis of genetically determined diseases such as Marfan syndrome [ 11 ] and congenital contractural arachnodactyly [ 12 ]. As reported previously, FBN1 protein was a large extracellular matrix glycoprotein that formed thread‐like microfibril filaments, which provided structural support for tissues, formed elastic fibers in the skin and vessels, regulated the availability of the transforming growth factor beta (TGF‐β) protein [ 13 , 14 , 15 , 16 , 17 ], and modulated the microenvironment [ 18 , 19 , 20 , 21 ].…”

Oxidative Stress in Plasma from Patients with Marfan Syndrome Is Modulated by Deodorized Garlic Preliminary Findings

“…Marfan syndrome (MFS) is a disorder of genetic origin with an autosomal dominant character that affects the gene that encodes for the fibrillin-1 protein (FBN-1), therefore altering connective tissue. It is associated with deformity and dysfunction of elastic fibers, which results in structural and functional damage to the structure of the aorta causing micro dissection of the middle layer and degeneration [ 1 ]. Damage to the aortic tissue in MFS is accompanied by oxidative stress (OS), vascular dysfunction, and loss of the contractile function and the endothelium-dependent relaxation [ 1 ].…”

“…It is associated with deformity and dysfunction of elastic fibers, which results in structural and functional damage to the structure of the aorta causing micro dissection of the middle layer and degeneration [ 1 ]. Damage to the aortic tissue in MFS is accompanied by oxidative stress (OS), vascular dysfunction, and loss of the contractile function and the endothelium-dependent relaxation [ 1 ].…”

A genome‐wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study

“…FBN2 is associated with congenital contractural arachnodactyly (Callewaert et al, 2009), with phenotypes including aortic root dilatation. The related gene FBN1 (located at 15q15‐21.3 [MIM: 134797]) is associated with Marfan syndrome (MIM: 154700) (Du et al, 2021), of which the phenotype includes interrupted aortic arch and atrial and ventricular septal defects, though further research is needed to determine whether there is a direct association between FBN1 and these subphenotypes. FBN2 is involved in the initial assembly of the aortic matrix and, with FBN1 , helps to guide the maturation of the aortic wall during fetal development and neonatal growth (Carta et al, 2006).…”