Darier-White disease ..., follicular keratosis (Darier-White disease, keratosis follicularis) - Gen ATP2A2.
Darier's disease (Darier-White or follicular keratosis) is a skin disorder manifested by the appearance of warty papules and malodorous plaques distributed on skin seborrheic (trunk, folds, scalp, arms, knees, front and area BTE ), by palmo-plantar depressions and nail dystrophy (striation). They may also be affected mucous membranes of the mouth, tongue, oral mucosa, gingiva and pharynx. Also described Acantholysis injuries with loss of cohesion of keratinocytes, as well as neurological and psychiatric disorders (depression, epilepsy, mental retardation, slow evolution progressive encephalopathy, learning disabilities and behavior). This disease usually occurs in late childhood or early adulthood
One type of Darier 's disease, known as the linear or segmental, is characterized by spots in localized areas of skin. Unlike the classical form, stains are not as widespread. Some people have linearly with nail abnormalities seen in people with the classic form of the disease, but these anomalies occur only on one side of the body.
This disease is due to mutations in the gene ATP2A2, located on the long arm of chromosome 12 (12q24.11). This gene encodes the enzyme SERCA2 (Sarcoplasmic / Endoplasmic Reticulum Calcium pumping ATPase type 2), which acts as a feed pump to control the calcium level positively charged ions (Ca2 +) in cells, maintaining a low concentration of Ca2 + in the cytoplasm, thereby obtaining energy for ATP hydrolysis. To achieve transports Ca2 + from the cytoplasm to the lumen of the endoplasmic reticulum and sarcoplasmic. Furthermore, the enzyme involved in the formation of intercellular bridges. Three isoforms of the enzyme, SERCA2a, SERCA2b and SERCA2c, differing in their carboxy - terminal domains and their tissue expression. Of these, SERCA2b is the predominant isoform in the skin. The endoplasmic reticulum cell involved in the processing and transport of proteins, while the sarcoplasmic reticulum is a muscle structure involved in muscle contraction and relaxation releasing and fixing calcium. Calcium ions act as signals for a large number of activities that are important for normal development and function of cells. This enzyme protein, SERCA2, allowing calcium ions to enter and exit the cells to respond to cellular signals.
They have identified more than 130 mutations in the gene ATP2A2 in people with the disease. Most of these mutations change the amino acids in SERCA2 enzyme. All mutations result in encoding a non - functional enzyme or its absence. A lack of enzyme SERCA2 reduces calcium concentrations in the endoplasmic reticulum and sarcoplasmic, so these are dysfunctional. It is believed that insufficient amounts of SERCA2 combined with external factors such as heat and minor injuries lead to signs and symptoms of Darier's disease. Although this enzyme is found throughout the body, it is unknown why almost exclusively affects the skin. Possibly because the enzyme in the skin SERCA2 can not be recycled so that their cells would be most vulnerable to the involvement of the enzyme.
This genetic disease is inherited as an autosomal dominant pattern which means that a single copy of the gene altered in each cell is sufficient for the alteration is manifested. In some cases the affected person inherits the mutation from an affected parent, but sometimes are new mutations without previous history in your family. The linear form of Darier disease usually not inherited but arises from mutations in the body cells produced after conception. These changes are called somatic mutations.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Darier's disease, by complete PCR amplification of exons ATP2A2 gene, 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).