title: Desmosomal genodermatoses.
abstract: Desmosomes are intercellular junctions that contribute to cell-cell adhesion, signalling, development and differentiation in various tissues, including the skin. Composed of a network of transmembranous and intracellular plaque proteins, pathogenic autosomal dominant or recessive mutations have been reported in 10 different desmosomal genes, resulting in a spectrum of phenotypes variably affecting skin, hair and heart. This review summarizes the molecular pathology and phenotypes that predominantly affect the skin/hair. Recent desmosomal genodermatoses described include lethal congenital epidermolysis bullosa (plakoglobin), cardiomyopathy with alopecia and palmoplantar keratoderma (plakoglobin), hypotrichosis with scalp vesicles (desmocollin 3), and generalized peeling skin disease (corneodesmosin). Understanding the range of clinical phenotypes in combination with knowledge of the inherent desmosome gene mutation(s) is helpful in managing and counselling patients, as well as providing insight into the biological function of specific components of desmosomes in skin and other tissues.
authors.affiliation: St John's Institute of Dermatology, King's College London (Guy's Campus), London SE1 9RT, UK.
authors.forename: G
authors.initials: G
authors.lastname: Petrof
authors.forename: J E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D051187:Desmocollins / Q000235:genetics; D051182:Desmogleins / Q000235:genetics; D051180:Desmoplakins / Q000235:genetics; D003896:Desmosomes / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D004820:Epidermolysis Bullosa / Q000145:classification; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D051191:Plakophilins / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics*; D051185:gamma Catenin / Q000235:genetics
chemical_list: C109656:CDSN protein, human; C081561:DSC2 protein, human; C490356:DSC3 protein, human; D051187:Desmocollins; D051182:Desmogleins; D051180:Desmoplakins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D051191:Plakophilins; D051185:gamma Catenin