Epidermolytic dystrophic bullosa autosomal recessive and autosomal dominant (epidermolysis bullosa Recessive Dystrophic -RDEB-) - COL7A1 gene.

Epidermolysis bullosa is a group of genetic disorders which cause skin is very fragile and easily blistering. Blisters and skin erosions form in response to injury or lower friction as rubbing or scratching. Dystrophic epidermolysis bullosa the (DEB) is one of the major forms of epidermolysis bullosa. Signs and symptoms of this disease vary widely among affected individuals. In mild cases, blisters may primarily affect the hands, feet, knees and elbows. In severe cases, affected individuals have widespread blisters that can cause vision loss, disfigurement, and other serious medical problems.

Dystrophic epidermolysis bullosa is classified into three main types. Although the types differ in severity, characteristics overlap significantly and are caused by mutations in the same gene:

  • Epidermolysis bullosa dystrophic autosomal recessive, Hallopeau-Siemens (RDEB-HS), which corresponds to the most serious and classic form of the disease type. Affected children are often born with widespread blistering and areas of absent skin, often caused by trauma during delivery. In general, the blisters are present throughout the body and affecting mucous membranes, such as the oral mucosa and the mucosa of the digestive tract. As blisters heal, lead to severe scarring. The scars on his mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Other healing complications may include fusion of the toes, loss of nails, contractures that restrict movement and eye inflammation that causes loss of vision. In addition, young adults with the classic form have a very high risk of developing squamous cell carcinoma, which tends to be unusually aggressive and is often fatal.
  • Autosomal recessive dystrophic epidermolysis bullosa, type no Hallopeau-Siemens (RDEB non-HS), which is somewhat less severe than the classic type shape and includes a variety of subtypes. Blisters are limited to the hands, feet, knees and elbows, but can spread to other areas in the most serious cases. People usually have misshapen nails. RDEB involves a non-HS scars in areas where blisters appear, but this form of the disease does not cause serious scarring characteristics of the conventional type.
  • Epidermolysis bullosa dystrophic autosomal dominant (DDEB). Signs and symptoms of this disease tend to be milder than those of autosomal recessive forms, blisters are usually limited to the hands, feet, knees and elbows. Blisters heal with scars, but they are less severe. Most affected people have deformed nails that can be lost over time. In milder cases, abnormal nails are the only sign of the disease.

The three major forms of dystrophic epidermolysis bullosa (recessive Hallopeau-Siemens-HS- -RDEB; recessive non-Siemens Hallopeau -RDEB non-HS-, and autosomal dominant type -DDEB) are due to mutations in the COL7A1 gene, located on the short arm of chromosome 3 (3p21.1). This gene encodes a protein that is used to assemble collagen type VII. Collagens, are molecules that give structure and strength to connective tissues throughout the body, such as skin, tendons and ligaments. Collagen type VII plays an important role in strengthening and stabilizing the skin. It is the main component structures called anchoring fibrils that anchor the epidermis to the dermis.

They have identified more than 400 mutations in the COL7A1 gene in dystrophic epidermolysis bullosa people. These mutations alter the structure or interrupt coding type VII collagen, impairs the ability of the anchoring fibrils to connect the epidermis to the dermis. When the type VII collagen is abnormal or absent, the anchoring fibrils are not formed properly. As a result, friction or other minor trauma can cause both skin layers are separated. This separation causes blistering, which can lead to extensive scarring as cured. Although it is unclear how mutations in the COL7A1 gene are associated with increased risk of certain cancers, especially squamous cell carcinoma in persons with severe types of dystrophic epidermolysis bullosa, it is believed that abnormal forms of collagen type VII retaining a fragment called the NC1 domain may increase the risk of tumor formation. Other studies, however, have not found this association.

The most serious types of dystrophic epidermolysis bullosa are inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. A milder form of dystrophic epidermolysis bullosa has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that a copy of the altered gene in each cell is sufficient to express the disease. About 70% of all people with dystrophic epidermolysis bullosa autosomal dominant inherited a COL7A1 gene altered from an affected parent. The remaining 30% of cases are caused by a new mutation in the COL7A1 gene. These cases occur in people with no history of disease in your family.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with dystrophic epidermolysis bullosa, by complete PCR amplification of exons COL7A1 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).