MITF

The MITF gene provides instructions for making a protein called microphthalmia-associated transcription factor. This protein plays a role in the development, survival, and function of certain types of cells. To carry out this role, the protein attaches to specific areas of DNA and helps control the activity of particular genes. On the basis of this action, the protein is called a transcription factor.

Microphthalmia-associated transcription factor helps control the development and function of pigment-producing cells called melanocytes. Within these cells, this protein also controls production of the pigment melanin, which contributes to hair, eye, and skin color. Melanocytes are also found in the inner ear and play an important role in hearing. Additionally, microphthalmia-associated transcription factor regulates the development of specialized cells in the eye called retinal pigment epithelial cells. These cells nourish the retina, the part of the eye that detects light and color. Some research indicates that microphthalmia-associated transcription factor also regulates the development of cells that break down and remove bone (osteoclasts) and cells that play a role in allergic reactions (mast cells).

Microphthalmia-associated transcription factor has a particular structure with three critically important regions. One region, known as the basic motif, binds to specific areas of DNA. Other regions, called the helix-loop-helix motif and the leucine-zipper motif, are critical for protein interactions. These motifs allow molecules of microphthalmia-associated transcription factor to interact with each other or with other proteins that have a similar structure. These interactions produce a two-protein unit (dimer) that functions as a transcription factor.

Waardenburg syndrome - caused by mutations in the MITF gene

Mutations in the MITF gene have been identified in some people with Waardenburg syndrome, type II. Some MITF mutations change the chemical building blocks (amino acids) used to make microphthalmia-associated transcription factor, which alters the helix-loop-helix or leucine-zipper motif. Other mutations result in an abnormally small version of microphthalmia-associated transcription factor. Researchers believe that both types of mutations disrupt the formation of dimers. Although some functional dimers are produced to serve as transcription factors, the amount is insufficient for full development of melanocytes. As a result, there is a shortage of melanocytes in certain areas of the skin, hair, eyes, and inner ear. This shortage leads to hearing loss and the patchy loss of pigmentation that are characteristic features of Waardenburg syndrome.

other disorders - caused by mutations in the MITF gene

MITF mutations also cause Tietz syndrome, which is characterized by profound hearing loss from birth, fair skin, and light-colored hair. The mutations either delete or change a single amino acid in the basic motif region of the MITF protein. As a result, the altered protein cannot bind to DNA, which affects the development of melanocytes and melanin production. The absence or reduced number of melanocytes in the inner ear leads to hearing loss. Decreased melanin production (hypopigmentation) accounts for the light skin and hair color that are characteristic of Tietz syndrome.