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Official Journal of the Italian Society of Dermatology and Sexually Transmitted Diseases
Indexed/Abstracted in: EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,014
Lai Cheong J. E., Wessagowit V., Fassihi H., McGrath J. A.
Genetic Skin Disease Group St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, London, UK
Kindler syndrome is a rare autosomal recessive genodermatosis that was first described in 1954. Clinically, the early features consist of trauma-induced skin blisters but later there is photosensitivity and poikiloderma. For years, this poorly understood condition was thought to be a variant of dystrophic epidermolysis bullosa or a congenital poikiloderma, or possibly the simultaneous occurrence of both disorders. In 2003, however, the genetic basis of Kindler syndrome was established. This inherited skin disease is caused by ablation of a novel protein, kindlin-1 (also known as kindlerin), encoded by the gene KIND1 on 20p12.3, and 19 different mutations (nonsense, frameshift or splice-site) have now been reported. Kindlin-1 is a 677-amino acid protein that is predominantly expressed in basal keratinocytes, where it provides a link between the actin microfilaments and the extracellular matrix, and forms part of focal contact junctions at the dermal-epidermal junction. The protein has functional domains involved in adhesion (via b integrin), other integrin-mediated cell activities such as cell spreading (e.g. in response to transforming growth factor-b), and cell signalling (possibly via PI3 kinase), although just how loss of kindlin-1 leads to the photobiological abnormalities seen in patients with Kindler syndrome is still a mystery. Nevertheless, the recent molecular findings have confirmed that Kindler syndrome is indeed a specific genodermatosis, and one which represents the first inherited skin disorder to involve a primary abnormality of the actin cytoskeleton-extracellular matrix complex. This review describes the clinico-pathological features of Kindler syndrome, the identification of the KIND1 gene, and the biological significance of the kindlin-1 protein.