Dystrophic epidermolysis bullosa (DEB) is a condition that has many sub-types, one of which is pretibial. The COL7A1 gene, which is responsible for producing VII collagen, is the cause of many of the subtypes of DEB. There are over 730 known mutations in this gene, and researchers are constantly striving to find more. The mutation that causes pretibial DEB has recently been discovered after a study was conducted with a family from China who all carry the gene. Researchers are excited, as discovering the root cause of the condition can help to diagnose and treat it.
About Dystrophic Epidermolysis Bullosa
Dystrophic epidermolysis bullosa (DEB) falls under the larger group of epidermolysis bullosa, which causes the skin to be very fragile and blister very easily. Minor injuries or friction can lead to blisters and skin erosions. DEB involves a great variety of signs and symptoms depending on the individual with this disorder. There are three major types of DEB, which vary in severity but are caused by mutations in the same gene. Two of these forms are autosomal recessive, which are Hallopeau-Siemens type (RDEB-HS) and non-Hallopeau-Siemens type (non-HS RDEB). The final form of this disease is the autosomal dominant type (DDEB). When considering all three types of this condition, the incidence is 6.5 per million births in the United States.
The COL7A1 gene is responsible for VII collagen, which gives strength and structure to connective tissue. It is necessary for strengthening and stabilizing skin, and it also helps to anchor the top layer of the skin, the epidermis, to the underlying level, the dermis. Mutations in this gene disrupt the production of collagen, therefore stopping the two layers of the skin from connecting. When this separation happens, there are blisters or skin erosions, which can lead to scarring. The more severe forms of this disease are carried in an autosomal recessive pattern, whereas the milder type is carried in an autosomal dominant pattern.
Symptoms vary depending on severity and type. Milder cases affect the hands, feet, knees, and elbows with blistering. More severe cases can lead to vision loss, disfigurement, and other serious medical conditions. In the RDEB-HS form, which is the most severe type, babies are born with severe blistering and areas of missing skin. Blisters are also present in the mouth and digestive tract. These blisters make it difficult to chew and swallow, which can lead to malnutrition. Other complications include fusions of the toes and fingers, the loss of finger and toe nails, inflammation of the eyes, and joint deformities. The non-HS RDEB type is less severe and involves blistering of the arms, legs, knees, and elbows. Scarring and malformed fingers and toes can occur as well. The last type, which is autosomal dominant, involves blistering that leads to less severe scarring. Malformed fingers are also common in this type, but at times only deformed finger or toe nails happen.
Doctors usually suspect DEB after seeing the condition of the skin. Lab tests like skin biopsies, genetic testing, and prenatal testing may also be conducted to confirm a diagnosis. Lifestyle changes and home care are the first steps of treatment. Medications to control itching and pain are also common in treatment. If infections arise, medication will be prescribed to treat that too. Surgery may be required for more severe cases as well. Procedures to widen the esophagus, graft skin, place a feeding tube, and restore mobility are all possibilities for treatment. Working with a physical or occupational therapist may also help to restore mobility that is lost due to joint deformities and scarring.
About the Discovery of the New Mutation
The discovery of a new mutation on the COL7A1 gene was found after a study was conducted on a family in the Anhui Province in China. A 23-year-old woman was noticed to have the symptoms of DEB on her pretibial area since birth. Despite the application of topical medication, the symptoms never went away and even progressed to the area around the initial site of blistering. Her family members also presented these symptoms with differing severity. A team of researchers wanted to investigate the cause behind the family’s symptoms. They conducted whole exome sequencing of DNA samples from the entire family and found that a missense mutation in the COL7A1 gene led to the pretibial dystrophic epidermolysis bullosa.
This new finding will allow healthcare professionals to better diagnose and treat those with DEB. Because different members of the family presented different levels of severity, researchers hypothesized that environmental factors or other levels of skin proteins could influence severity. This hypothesis requires further research, which will hopefully improve diagnose and treatment as well.
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