Disorders of the cutaneous basement membrane zone--the paradigm of epidermolysis bullosa.

[kindler syndrome]

The cutaneous basement membrane zone (BMZ ) is a highly specialized functional complex that provides the skin with structural adhesion and resistance to shearing forces . Its regulatory functions include control of epithelial-mesenchymal interactions under physiological and pathological conditions . Mutations in genes encoding components of the BMZ are associated with inherited skin disorders of the epidermolysis bullosa (EB ) group , characterized by skin fragility , mechanically induced blisters and erosions of the skin and mucous membranes . Although most disease-associated genes are known , the genetic basis of new EB subtypes linked to mutations in genes for focal adhesion proteins was uncovered only recently . The molecular mechanisms leading to blistering , abnormal wound healing , predisposition to skin cancer , and other complications in EB have been elucidated using animal models and disease proteomics . The rapid progress in understanding the molecular basis of EB has enabled the development of strategies for biologically valid causal therapies .