Junctional epidermolysis bullosa (JEB) is a rare genetic disorder that falls under the broader epidermolysis bullosa (EB) category. EB comprises a group of inherited skin disorders characterized by blistering and skin fragility in response to minor trauma or friction. JEB involves explicitly abnormalities in the proteins that help anchor the layers of the skin together. JEB is the rarest type of EB, with an incidence of 2.7 cases per 1.000.000 live births.
Junctional epidermolysis bullosa genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Critical features of Junctional Epidermolysis Bullosa include:
- Blisters and Skin Erosions: Individuals with JEB experience blistering and skin erosions, often in response to minor trauma or friction. Blisters can occur on the skin and mucous membranes, such as in the mouth and digestive tract.
- Skin Fragility: The skin is fragile and prone to tearing, leading to open wounds and ulcers.
- Scarring: Healing wounds in JEB can result in scarring, and repeated blistering and scarring may lead to contractures, limiting joint mobility.
- Oral Involvement: Blistering and erosions can occur in the mouth, making eating and swallowing challenging. Dental abnormalities may also be present.
- Respiratory Complications: In severe cases, JEB may affect the respiratory tract, leading to respiratory complications. This can be life-threatening.
- Nail and Hair Abnormalities: Individuals with JEB may have nail and hair abnormalities.
JEB is caused by mutations in genes that encode proteins critical for the structure and function of the basement membrane zone, where the epidermis (outer layer of the skin) attaches to the underlying dermis. Mutations in the LAMA3, LAMB3, and LAMC2 genes are associated with various forms of JEB.
Junctional epidermolysis bullosa is inherited in an autosomal recessive manner, meaning that affected individuals inherit two mutated copies of the relevant gene (one from each parent). The severity of symptoms can vary widely, and there are different subtypes of JEB.
Management of JEB involves supportive care to address the symptoms and complications. This may include wound care, management of blistering and scarring, nutritional support, and, in severe cases, respiratory support.
Genetic counseling is essential for families affected by JEB to understand the inheritance pattern, assess the risk of having affected children, and discuss family planning options.
More Information
JEB may be caused by mutations in several genes, including LAMB3 (70% of all JEB), COL17A1 (12%), LAMC2 (9%), and LAMA3 (9%). The LAMB3 gene, the most common, encodes for laminin beta-3, a basement membrane protein. Since EBJ follows an autosomal recessive mode of inheritance, two copies of the same mutation are required for the disease to occur. However, compound heterozygotes (patients with two different mutations in heterozygosis) have also been observed.
The c.1903C>T and c.124C>T mutations in the LAMB3 gene are frequent in Caucasian patients with JEB. Both cause the appearance of an early stop codon and consequent loss of protein function. It is estimated that the c.124C>T and c.1903C>T mutations account for 50% of LAMB3 mutant alleles.
Junctional epidermolysis bullosa genetic testing analyzes the 6 most frequent pathogenic mutations of the LAMB3 gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
