What are the genetic changes related to autosomal dominant hyper-IgE syndrome ?
Mutations in the STAT3 gene cause most cases of AD-HIES. This gene provides instructions for making a protein that plays an important role in several body systems. To carry out its roles, the STAT3 protein attaches to DNA and helps control the activity of particular genes. In the immune system, the STAT3 protein regulates genes that are involved in the maturation of immune system cells, especially T cells. These cells help control the body's response to foreign invaders such as bacteria and fungi.  Changes in the STAT3 gene alter the structure and function of the STAT3 protein, impairing its ability to control the activity of other genes. A shortage of functional STAT3 blocks the maturation of T cells (specifically a subset known as Th17 cells) and other immune cells. The resulting immune system abnormalities make people with AD-HIES highly susceptible to infections, particularly bacterial and fungal infections of the lungs and skin. The STAT3 protein is also involved in the formation of cells that build and break down bone tissue, which could help explain why STAT3 gene mutations lead to the skeletal and dental abnormalities characteristic of this condition. It is unclear how STAT3 gene mutations lead to increased IgE levels.  When AD-HIES is not caused by STAT3 gene mutations, the genetic cause of the condition is unknown.