title: Genetically induced abnormalities of epidermal differentiation and ultrastructure in ichthyoses and epidermolyses: pathogenesis, heterogeneity, fetal manifestation, and prenatal diagnosis.
abstract: Comparative ultrastructural investigations on the pathomorphogenesis of inherited ichthyoses and epidermolyses have shown that such heterogeneous skin disorders may serve as model systems for genetic interactions with developmental processes, such as keratinization, or functional systems, such as dermal-epidermal junctional integrity. Most interesting from the morphologic point of view are dominantly inherited skin disorders in the ichthyosis and epidermolysis bullosa groups in which primary structural defects of structural proteins have been demonstrated that seem to be under the direct control of the mutant gene. Such structural abnormalities concern keratohyalin in autosomal-dominant ichthyosis vulgaris, the tonofilament system in hystrix-like ichthyoses, and the anchoring fibrils in dominant dystrophic epidermolyses. Taking bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) as a central example, we discuss the stability of such structural defects, the heterogeneity in the ultrastructural abnormalities of clinically closely similar entities (ichthyosis hystrix Curth-Macklin, congenital reticulate ichthyosiform erythroderma), and, in the latter keratinization disorder, the presence of an unusual filament system of unknown biochemical composition in the abnormal keratinocytes. Expression of mutant genes during fetal life and fetal manifestation of such abnormalities are a precondition for the prenatal diagnosis of genetic skin disorders (bullous ichthyosiform erythroderma, epidermolysis bullosa dystrophica Hallopeau-Siemens, Herlitz syndrome). Finally, problems related to the differentiation of mutant keratinocytes and of amniotic fluid cells of fetuses at risk of genetic skin disorders under the in vitro conditions of primary cell cultures are briefly discussed.
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004820:Epidermolysis Bullosa / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D005333:Fetus / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007057:Ichthyosis / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011487:Protein Conformation; D011506:Proteins / Q000235:genetics
chemical_list: D011506:Proteins