title: Translational benefits from research on rare genodermatoses.
abstract: Significant new discoveries about many of the genodermatoses have been made recently through an improved knowledge of the human genome, advances in molecular screening strategies and also through more comprehensive Internet DNA databases. By 2003, over 350 single gene skin disorders had been characterized at a molecular level. These new data provide more detailed information for patients, allow for more accurate diagnoses, and help improve genetic counselling. Other benefits include the feasibility of carrier screening and DNA-based prenatal testing, as well as a platform for devising new treatments, including somatic gene therapy. Research on rare single gene disorders also provides new insight into more common skin conditions. For example, new ideas about photosensitivity are emerging from discoveries of mutations in a novel component of the actin cytoskeleton (kindlin-1) in the rare inherited poikiloderma disorder, Kindler syndrome. Likewise, new clues to understanding disease pathology in lichen sclerosus have been gleaned from the discovery of pathogenic mutations in the skin protein, extracellular matrix protein 1, in the rare sclerosing inherited skin disorder, lipoid proteinosis. Finally, new insight into what can cause exuberant granulation tissue in chronic wounds has been provided by the discovery of specific mutations in the basement membrane protein, laminin 5, in the rare inherited condition, laryngo-onychocutaneous syndrome. It is clear that a precise research focus on the rare genodermatoses is providing practical benefits for sufferers of these disorders, as well as new lessons and ideas about more common acquired skin conditions.
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospital's Medical School, Lambeth Palace Road, London SE1 7EH, UK. john.mcgrath@kcl.ac.uk
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D030561:Databases, Nucleic Acid; D005820:Genetic Testing; D015316:Genetic Therapy; D015894:Genome, Human; D006801:Humans; D009154:Mutation / Q000235:genetics; D012873:Skin Diseases, Genetic / Q000235:genetics*