Chronic benign pemphigus; Hailey-Hailey disease (Benign chronic pemphigus) - Gen ATP2C1

Benign chronic pemphigus, also known as Hailey-Hailey disease of, is a rare involvement of the skin that usually appears in early adulthood. This disease is characterized by red areas and blisters occur more frequently in skin folds, such as the groin, axilla, neck and under the breasts. These can produce swollen areas crusts or scales and can be pruritic and burning. The skin problems tend to be aggravated by exposure to moisture, such as perspiration, friction and heat.

The severity of chronic benign pemphigus varies from relatively mild episodes of skin irritation to extensive areas of skin and persistent without epidermis and blisters that interfere with daily activities. The affected skin may become infected with bacteria or fungi, which causes pain and odor. Although the condition is described as benign or noncancerous, in rare cases, the skin lesions can become squamous cell carcinoma. Many affected individuals also have white lines along their nails. These lines do not cause any health problems, but may be useful for the diagnosis of chronic benign pemphigus.

This process is due to mutations in the ATP2C1 (Ca2 + ATPase secretory pathway Transporting 1) gene, located on the long arm of chromosome 3 (3q22.1). The gene encodes ATP2C1 synthesis hSPCA1 protein, found in many cell types. The hSPCA1 protein helps cells to store calcium. Specifically, the protein carries hSPCA1 calcium ions in the Golgi apparatus, where they are stored until needed. Storage and adequate calcium release is essential for many cellular activities, including regulation of growth, division and cell adhesion. The hSPCA1 protein appears to be particularly important for the normal function of keratinocytes, which are found in the epidermis. The protein also carries hSPCA1 manganese ions in the Golgi apparatus. Manganese acts with a variety of enzymes and is involved in processing new encoded proteins.

They described over 136 mutations in the gene ATP2C1 in people with chronic benign pemphigus. Some of these mutations consist nonsense mutations (62), mutations cutting and joining - splicing - (21), small deletions (36), larger deletions (4), small insertions (9), and complex rearrangements (3). Mutations in this gene reduce the amount of functional protein hSPCA1, which affect storage of calcium ions in the Golgi apparatus. For unknown reasons, this abnormal calcium storage affects more than other cell types keratinocytes. Problems with calcium regulation impair many cellular functions, including cell adhesion. As a result, keratinocytes are not strongly adhered to each other, which causes the skin to become brittle and less resistant to minor trauma. While mutations of genes ATP2C1 probably also affect the transport of manganese within the cells, it is not believed that the abnormal regulation of manganese contributes to the signs and symptoms of chronic benign pemphigus.

This process is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with chronic benign pemphigus, by complete PCR amplification of the exons of the gene ATP2C1, 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).