The genetics of skin fragility

• Published in: Annual review of genomics and human genetics Vol. 15; p. 245
• Main Authors: Has, Cristina, Bruckner-Tuderman, Leena
• Format: Journal Article
• Language: English
• Published: United States 01.01.2014
• Subjects: Epidermis - pathology; Epidermolysis Bullosa - genetics; Epidermolysis Bullosa - pathology; Genetic Association Studies; Genetic Therapy; Humans; Mutation; Phenotype; Skin - metabolism; Skin - pathology; Translational Medical Research; basement membrane; Kindler syndrome; epidermolysis bullosa; blister; cell adhesion
• ISSN: 1545-293X
• DOI: 10.1146/annurev-genom-090413-025540

Genetic skin fragility manifests with diminished resistance of the skin and mucous membranes to external mechanical forces and with skin blistering, erosions, and painful wounds as clinical features. Skin fragility disorders, collectively called epidermolysis bullosa, are caused by mutations in 18 distinct genes that encode proteins involved in epidermal integrity and dermal-epidermal adhesion. The genetic spectrum, along with environmental and genetic modifiers, creates a large number of clinical phenotypes, spanning from minor localized lesions to severe generalized blistering, secondary skin cancer, or early demise resulting from extensive loss of the epidermis. Laboratory investigations of skin fragility have greatly augmented our understanding of genotype-phenotype correlations in epidermolysis bullosa and have also advanced skin biology in general. Current translational research concentrates on the development of biologically valid treatments with therapeutic genes, cells, proteins, or small-molecule compounds in preclinical settings or human pilot trials.