title: Progress in epidermolysis bullosa: the phenotypic spectrum of plectin mutations.
abstract: Plectin, a large multidomain adhesive protein with versatile binding functions, is expressed in a number of tissues and cell types. In the skin, plectin is a critical component of hemidesmosomes, interacting with keratin intermediate filaments and beta4 integrin. Mutations in the plectin gene (PLEC1) result in fragility of skin, demonstrating blister formation at the level of hemidesmosomes. These blistering disorders belong to the spectrum of epidermolysis bullosa (EB) phenotypes, and three distinct variants because of plectin mutations have been identified. First, EB with muscular dystrophy, an autosomal recessive syndrome, is frequently caused by premature termination codon-causing mutations leading to the absence of plectin both in the skin and in the muscle. Second, a heterozygous missense mutation (R2110W) in PLEC1 has been documented in patients with EB simplex of the Ogna type, a rare autosomal dominant disorder. Finally, recent studies have disclosed plectin mutations in patients with EB with pyloric atresia, an autosomal recessive syndrome, frequently with lethal consequences. Collectively, these observations attest to the phenotypic spectrum of plectin mutations, and provide the basis for accurate genetic counselling with prognostic implications, as well as for prenatal diagnosis in families at the risk of recurrence of the disease.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, and DebRA Molecular Diagnostics Laboratory, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: E
authors.initials: E
authors.lastname: Pfendner
authors.forename: F
authors.initials: F
authors.lastname: Rouan
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D003062:Codon; D003896:Desmosomes / Q000378:metabolism; D004820:Epidermolysis Bullosa / Q000175:diagnosis* / Q000235:genetics*; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000502:physiology; D008957:Models, Genetic; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D051190:Plectin
chemical_list: D003062:Codon; D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051190:Plectin