Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome

Abstract

Background Marfan syndrome (MFS) is a multi‐systemic autosomal dominant disease of the connective tissue characterized by the early development of thoracic aneurysms/dissections, along with various manifestations of the ocular and skeletal systems. Due to the genetic and clinical heterogeneity, the clinical diagnosis of this disorder is challenging. Loss‐of‐function mutations in FBN1 (encodes fibrillin‐1) lead to MFS type 1. Also, similar mutations in transforming growth factor β receptor 2 ( TGFBR2) gene cause MFS type 2. Both proteins involve in TGF‐β signaling. Methods In this study, genetic screening using a panel involving 14 genes, especially FBN1 and TGFBR2 , were performed on seven representatives affected members of seven unrelated Iranian families suspected with MFS. To confirm the variants, Sanger sequencing was applied to other affected/unaffected members of the families. Results A total of 13 patients showed MFS manifestations. Using genetic screening, two novel and three previously reported variants in FBN1 were identified. We also detected two variants (a novel and a previously reported variant) in the TGFBR2 gene. Conclusion In this study, we introduce three novel variants identified through gene screening in seven Iranian MFS families. This report is expected to considerably improve genetic counseling for Iranian MFS families. Early precise molecular diagnosis can be helpful for better management and improving the life expectancy of these patients.

SMAD4 contributes to chondrocyte and osteocyte development

“…TGF‐β needs the SMAD family to function normally, and it stimulates a variety of physiological processes such as tissue repair, cell growth, cell differentiation and cell proliferation. 60 , 61 TGF‐β activates two types of receptors including the activin receptor‐like kinase 1 (ALK1) and ALK5. TGF‐β stimulates (using ALK1) or inhibits (via ALK5) the migration and proliferation of endothelial cells.…”

Understanding Musculoskeletal Disorders Through Next-Generation Sequencing

“…Identification of FBN1 variants by WES substantiates the potential of NGS technologies. Several other studies have also identified genetic variants in FBN1 and FBN2 independently in different populations 21-24 . Fibrillin-1 is a structural macromolecule that polymerizes into microfibrils; multiple mouse models have shown the functional importance of FBN1 gene variants 25 .…”