How LAMB3 gene cause Junctional Epidermolysis Bullosa?
Mutation in LAMB3 gene causes Junctional Epidermolysis
Bullosa [JEB].
More than 80 mutations in the LAMB3 gene have
been identified in people with JEB. The more severe form of the disease, known
as ‘Herlitz JEB’, usually results from mutations that severely disrupt the
production of functional ‘laminin 332’. Most of these mutations lead to a
premature stop signal in the instructions for making the beta 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
other 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 LAMB3 gene mutations cause the milder
form of JEB — ‘non-Herlitz JEB’. Some of these mutations alter single protein
building blocks (amino acids) in the beta subunit of laminin 332. Others add or
delete a small number of amino acids in the beta (β) subunit or change the gene's instructions to make the subunit. The genetic changes
responsible for non-Herlitz JEB usually lead to the production of a defective laminin 332
protein. Affected individuals experience
blistering but it may be limited to the hands, feet, knees, and elbows and
often improves after the newborn period.
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