transforming growth factor beta 2
The TGFB2 gene provides instructions for producing a protein called transforming growth factor beta-2 (TGFβ-2). This protein is found throughout the body and is required for development before birth and throughout life. To carry out its functions, TGFβ-2 attaches (binds) to receptor proteins on the surface of cells. This binding triggers the transmission of signals within cells, controlling various cellular activities. As part of a signaling pathway called the TGF-β pathway, the TGFβ-2 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and controlled cell death (apoptosis). Because the TGFβ-2 protein keeps cells from growing and dividing too rapidly or in an uncontrolled way, it can suppress the formation of tumors.
The TGFβ-2 protein plays a role in the formation of blood vessels, the regulation of muscle tissue and body fat development, wound healing, and immune system function. TGFβ-2 is especially abundant in tissues that make up the skeleton, where it helps regulate bone growth, and in the intricate lattice that forms in the spaces between cells (the extracellular matrix).
At least 20 mutations in the TGFB2 gene have been found to cause Loeys-Dietz syndrome type IV. This disorder affects connective tissue, which gives structure and support to blood vessels, the skeleton, and many other parts of the body. Loeys-Dietz syndrome type IV is characterized by blood vessel abnormalities, heart defects, and skeletal deformities. The TGFB2 gene mutations that cause this condition lead to the production of a TGFβ-2 protein with little or no function. As a result, the protein cannot bind to its receptors. Although the TGFβ-2 protein and its receptors are not bound, TGF-β pathway signaling occurs at an even greater intensity than normal. Researchers speculate that the activity of other proteins in this signaling pathway is increased to compensate for the reduction in TGFβ-2 activity; however, the exact mechanism responsible for the increase in signaling is unclear. The overactive signaling pathway disrupts development of connective tissue and various body systems and leads to the signs and symptoms of Loeys-Dietz syndrome type IV.
A few mutations have been found that delete the entire TGFB2 gene and some nearby genetic material. People with these deletions often have the features of Loeys-Dietz syndrome as well as features not usually associated with the condition, such as intellectual disability and movement problems. Researchers are working to determine which genes are missing as a result of these deletions and how their loss contributes to these additional signs and symptoms.