MOLECULAR-BASIS OF DYSTROPHIC EPIDERMOLYSIS-BULLOSA - MUTATIONS IS THE TYPE-VII COLLAGEN GENE (COL7A1)

Epidermolysis bullosa (EB), a group of heritable blistering diseases c haracterized by tissue separation within the cutaneous basement membra ne zone, is inherited either in an autosomal dominant or autosomal rec essive fashion. EB has been divided into four broad categories based o n the precise level of tissue separation, In the dystrophic forms of E B (DEB), tissue separation occurs below the lamina densa within the up per papillary dermis at the level of anchoring fibrils, which are freq uently altered in morphology, reduced in number, or entirely absent. S ince type VII collagen is the major component of anchoring fibrils, th e corresponding gene, COL7A1, was proposed as the candidate for DEB. S ubsequent cloning of COL7A1 and elucidation of its genomic structure h ave led to identification of 53 distinct mutations in COL7A1 reported thus far. These mutations consist of nonsense mutations, small inserti ons or deletions resulting in frameshift and premature termination cod ons, splice site mutations, or missense mutations, particularly glycin e substitutions within the collagenous domain of the protein. The type s and combinations of these mutations and their positions along the ty pe VII collagen molecule result in a spectrum of phenotypic severity a nd determine the mode of inheritance. Thus, examination of the mutatio n database has allowed genotype/phenotype predictions, with an impact on genetic counseling in this group of genodermatoses. (C) 1997 Wiley- Liss, Inc.