EDARADD

The EDARADD gene provides instructions for making a protein called the EDAR-associated death domain protein. This protein is part of a signaling pathway that plays an important role in development before birth. Specifically, it is critical for interactions between two embryonic cell layers called the ectoderm and the mesoderm. In the early embryo, these cell layers form the basis for many of the body's organs and tissues. Ectoderm-mesoderm interactions are essential for the formation of several structures that arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.

The EDARADD protein interacts with another protein, called the ectodysplasin A receptor, which is produced from the EDAR gene. This interaction occurs at a region called the death domain that is present in both proteins. The EDARADD protein acts as an adapter, which means it assists the ectodysplasin A receptor in triggering chemical signals within cells. These signals affect cell activities such as division, growth, and maturation. Before birth, this signaling pathway controls the formation of ectodermal structures such as hair follicles, sweat glands, and teeth.

hypohidrotic ectodermal dysplasia - caused by mutations in the EDARADD gene

A mutation in the EDARADD gene is an infrequent cause of the autosomal recessive form of hypohidrotic ectodermal dysplasia. With autosomal recessive inheritance, two copies of the EDARADD gene are mutated in each cell.

The EDARADD mutation responsible for hypohidrotic ectodermal dysplasia changes a single protein building block (amino acid) in the EDARADD protein. This genetic change replaces the amino acid glutamine with the amino acid lysine at protein position 142 (written as Glu142Lys). Because this mutation occurs in the death domain, it prevents the EDARADD protein from interacting effectively with the ectodysplasin A receptor. As a result, the receptor probably cannot trigger signals needed for ectoderm-mesoderm interactions and the normal development of hair follicles, sweat glands, and other ectodermal structures. This disruption in ectodermal development leads to the characteristic features of hypohidrotic ectodermal dysplasia.