The TGM1 gene provides instructions for making an enzyme called transglutaminase 1. This enzyme is found in cells that make up the outermost layer of the skin (the epidermis). Transglutaminase 1 is involved in the formation of the cornified cell envelope, which is a structure that surrounds skin cells and helps form a protective barrier between the body and its environment. Specifically, transglutaminase 1 forms strong bonds, called cross-links, between the structural proteins that make up the cornified cell envelope. This cross-linking provides strength and stability to the epidermis.
Many mutations in the TGM1 gene have been found to cause lamellar ichthyosis, which is a condition that causes scaly skin that covers much of the body, and other skin abnormalities. Some TGM1 gene mutations that cause this condition change single DNA building blocks (nucleotides) in the transglutaminase 1 enzyme. The most frequently occurring mutation (written as 877-2A>G) affects the way the gene's instructions are pieced together to form the enzyme and results in an abnormally shortened, nonfunctional enzyme. Other TGM1 gene mutations result in a transglutaminase 1 enzyme that cannot function normally, is abnormally short, or is not produced. A lack of functional transglutaminase 1 prevents the formation of the cornified cell envelope, causing the skin abnormalities of lamellar ichthyosis.
In addition to lamellar ichthyosis (described above), TGM1 gene mutations have been found to cause other forms of ichthyosis. In one type, called self-healing collodion baby, affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane usually dries and peels off during the first few weeks of life, and affected infants often show near normal skin within a few months. Another type of ichthyosis, called bathing suit ichthyosis, is characterized by scaly skin that is limited to the trunk.
- epidermal TGase
- protein-glutamine gamma-glutamyltransferase K
- TGase K
- transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase)
- transglutaminase K
- transglutaminase, keratinocyte