What are the genetic changes related to arterial tortuosity syndrome ?
Arterial tortuosity syndrome is caused by mutations in the SLC2A10 gene. This gene provides instructions for making a protein called GLUT10. The level of GLUT10 appears to be involved in the regulation of a process called the transforming growth factor-beta (TGF-) signaling pathway. This pathway is involved in cell growth and division (proliferation) and the process by which cells mature to carry out special functions (differentiation). The TGF- signaling pathway is also involved in bone and blood vessel development and the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells and defines the structure and properties of connective tissues.  SLC2A10 gene mutations that cause arterial tortuosity syndrome reduce or eliminate GLUT10 function. By mechanisms that are not well understood, a lack (deficiency) of functional GLUT10 protein leads to overactivity (upregulation) of TGF- signaling. Excessive growth signaling results in elongation of the arteries, leading to tortuosity. Overactive TGF- signaling also interferes with normal formation of the connective tissues in other parts of the body, leading to the additional signs and symptoms of arterial tortuosity syndrome.