EDN3

The EDN3 gene provides instructions for making a protein called endothelin 3. Proteins in the endothelin family are produced in various cells and tissues, where they are involved in the development and function of blood vessels, the production of certain hormones, and the stimulation of cell growth and division.

Endothelin 3 functions by interacting with another protein, endothelin receptor B, on the surface of cells. During embryonic development, endothelin 3 and endothelin receptor B play an important role in cells called neural crest cells. These cells migrate from the developing spinal cord to specific regions in the embryo, where they give rise to many different types of cells. In particular, endothelin 3 and its receptor are essential for the formation of nerves in the large intestine (enteric nerves) and melanocytes. Melanocytes are cells that produce melanin, a pigment that contributes to skin, hair, and eye color. Melanin is also involved in the normal function of the inner ear.

Waardenburg syndrome - caused by mutations in the EDN3 gene

Several mutations in the EDN3 gene have been identified in people with Waardenburg syndrome, type IV (also known as Waardenburg-Shah syndrome). This type of Waardenburg syndrome is characterized by changes in skin, hair, and eye coloring; hearing loss; and an intestinal disorder called Hirschsprung disease that causes severe constipation or intestinal blockage. EDN3 mutations change single DNA building blocks (nucleotides) in the gene, preventing the production of a functional endothelin 3 protein. Because active endothelin 3 is necessary for the formation of enteric nerves and melanocytes, these cell types do not form normally during embryonic development. Missing enteric nerves in certain parts of the intestine cause the signs and symptoms of Hirschsprung disease. A lack of melanocytes affects the coloring of skin, hair, and eyes and causes the hearing loss characteristic of Waardenburg syndrome.

other disorders - caused by mutations in the EDN3 gene

A small number of mutations in the EDN3 gene are responsible for Hirschsprung disease in people without Waardenburg syndrome. These mutations change one nucleotide or insert an additional nucleotide in the gene. Changes in the EDN3 gene disrupt the normal function of endothelin 3, preventing it from playing its usual role in the development of enteric nerves. As a result, these cells do not form normally during embryonic development. A lack of enteric nerves prevents stool from moving through the intestines normally, leading to severe constipation and intestinal blockage.