ZNF341

Autosomal dominant hyper-IgE syndrome

At least five mutations in the ZNF341 gene have been found to cause a condition similar to autosomal dominant hyper-IgE syndrome (AD-HIES), which is a disorder of the immune system characterized by recurrent skin and lung infections and abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. AD-HIES is usually caused by STAT3 gene mutations and follows an autosomal dominant pattern of inheritance, which means one altered copy of the gene is sufficient to cause the disorder. In contrast, the condition caused by ZNF341 gene mutations follows an autosomal recessive pattern of inheritance, which means both copies of the gene must be altered for immune system problems to develop.

The ZNF341 gene mutations that cause an AD-HIES-like condition result in production of an abnormally short ZNF341 protein or production of no protein. With little or no ZNF341 protein, production of the STAT1 and STAT3 proteins is impaired. 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. A shortage of STAT1 protein is not thought to contribute to immune system problems in affected individuals.