Piebaldism (piebaldism) - Genes KIT and SNAI2.
Piebaldism is a disorder characterized by the absence of melanocytes in certain areas of the skin and hair. Melanocytes produce the pigment melanin, which contributes to the color of hair, eyes and skin. The absence of melanocytes develop depigmented patches on the skin and hair coloring. Approximately 90 percent of those affected have a section of white hair near your front hairline. Eyelashes, eyebrows and skin near the front hairline may also lack pigmentation.
Usually, people with piebaldism have other non - pigmented skin areas that appear symmetrically on both sides. There may be areas of pigmented skin within or around the edges of non - pigmented areas. In most cases, non - pigmented areas are present at birth and do not increase in size or number. Pigmented areas have a higher risk of sunburn and skin associated with excessive sun exposure cancer.
This process is due to mutations in the KIT gene and SNAI2. Piebaldism may also be a feature of other diseases such as Waardenburg syndrome. These alterations have other genetic causes and other signs and symptoms.
The KIT gene, located on the long arm of chromosome 4 (4q12), encoding a protein belonging to a family of proteins called tyrosine kinase receptors. Receptor tyrosine kinases transmit signals from cell surface into the cell through a process called signal transduction. The protein is found in the cell membrane of certain cell types where specific protein called stem cell factor, it binds to it. This binding other proteins within the cell is activated by adding a group of oxygen and phosphorus atoms in specific positions. This process, called phosphorylation leads to activation of a number of proteins in multiple signaling pathways. Signaling pathways stimulated by control of the protein result in many important cellular processes such as growth and proliferation, survival, and migration. Signaling protein is important for the development of certain types of cells, including germ cells, hematopoietic stem cells, mast cells, cells in the gastrointestinal tract, and melanocytes. Melanocytes produce melanin pigment, which contributes to the color of hair, eyes and skin.
They have identified at least 69 mutations in the KIT gene in people with piebaldism. Mutations result in a nonfunctional protein of the KIT gene. It is believed that the loss of KIT signaling interrupts the growth, proliferation and migration of melanocytes during development, resulting in skin patches lacking pigmentation.
The SNAI2 gene, located on the long arm of chromosome 8 (8q11) encodes a protein called snail 2. Research indicates that the protein is required during embryonic development growth of cells from the neural crest. These cells migrate from the developing spinal cord to specific regions in the embryo and give rise to many tissues and cell types, including melanocytes. Scroll 2 protein likely plays a role in the formation and survival of melanocytes.
Mutations in the gene cause SNAI2 the loss of one copy of the gene, which reduces the production of the protein shell 2. The shortage of the protein shell 2 can alter the development of melanocytes in certain areas of the skin and hair, causing irregular pigment loss.
Piebaldism is inherited as an autosomal dominant, which means a copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has a parent with the condition.
Tests in IVAMI: in IVAMI perform detection of mutations associated with piebaldism, by complete PCR amplification of the exons of the KIT and SNAI2, respectively genes and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).