LAMA3 gene cause JEB

How LAMA3 gene cause Junctional Epidermolysis Bullosa?

Mutation in LAMA3 gene causes Junctional Epidermolysis Bullosa [JEB]. More than 30 mutations in the LAMA3 gene have been identified in people with junctional epidermolysis bullosa (JEB). The more severe form of the disease, known as ‘Herlitz JEB’, usually results from mutations which severely disrupt the production of functional ‘laminin 332’. Most of these mutations lead to a premature stop signal in the instructions for making the alpha (α) subunit of laminin 332, which prevents the assembly of this protein. Without laminin 332 the epidermis is weakly connected to the underlying layers of skin. Friction or any minor trauma (such as rubbing or scratching) can cause the skin layers to separate, leading to the formation of blisters. Infants with Herlitz JEB develop widespread blistering that causes life-threatening complications.

Other LAMA3 gene mutations cause the milder form of junctional epidermolysis bullosa, ‘non-Herlitz JEB’. Some of these mutations alter single protein building blocks (amino acids) in the alpha (α) subunit of laminin 332. Others add or delete a small number of amino acids in the alpha (α) subunit or change the way the gene's instructions are used to make the subunit. The genetic changes responsible for non-Herlitz JEB usually lead to the production of a laminin 332 protein which retains some of its function. Affected individuals experience blistering, but it may be limited to the hands, feet, knees, and elbows and often improves after the newborn period.

Source: www.ghr.nlm.nih.gov