INHERITED SKIN DISEASES - NEW GENETIC APPROACHES

New powerful techniques capable of effective genome analysis are now available for the study of inherited skin disorders. In most instances, a biochemical defect in the patient points to the responsibility of a given gene in the occurrence of the disease. The role of this candidate gene is tested by genetic linkage studies, then confirmed by identification of the molecular gene defect and collection of evidence that this gene defect is causally related to the disease phenotype. This conventional genetic approach has succeeded in identifying the genes and molecular defects responsible for X-linked ichtyosis, epidermolysis bullosa simplex of Koebner and Dowling-Meara, albinism and piebaldism. When no biochemical clue is available, reverse genetics can be used to delineate the region of the genome that contains the disease locus, thus shortening the search for the candidate gene. This approach, occasionally aided by the presence of cytogenetic anomalies, has allowed to locate and identify the gene for Von Recklinghausen neurofibromatosis (NF1) and to demonstrate the existence of two loci genetically related to tuberous sclerosis.