title: Identification of a lethal form of epidermolysis bullosa simplex associated with a homozygous genetic mutation in plectin.
abstract: Genetic mutations in plectin, a cytoskeleton linker protein expressed in a large variety of tissues including skin, muscle, and nerves, cause epidermolysis bullosa simplex with muscular dystrophy, a recessive inherited disease characterized by blistering of the skin and late onset of muscular dystrophy, and Ogna epidermolysis bullosa simplex, a rare dominant inherited form of epidermolysis bullosa simplex with no muscular involvement. Here we report a novel homozygous genetic mutation (2727del14) in the plectin gene (PLEC1) associated with a lethal form of recessive inherited epidermolysis bullosa in a consanguineous family with three affected offspring. This new clinical variant of epidermolysis bullosa is characterized by general skin blistering, aplasia cutis of the limbs, developmental complications, and rapid demise after birth. Mutation 2727del14 is the first genetic defect described in PLEC1 that disrupts the plakin domain of plectin. The severe phenotype of the patients may be linked to the role of the N-terminal domain in the function of plectin and develops the understanding of the genotype-phenotype correlations in the genodermatoses affecting the dermal-epidermal junction.
authors.affiliation: INSERM U385, Faculté de Médecine, Nice, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Charlesworth
authors.forename: Laurent
authors.initials: L
authors.lastname: Gagnoux-Palacios
authors.forename: Maryse
authors.initials: M
authors.lastname: Bonduelle
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Ortonne
authors.forename: Linda
authors.initials: L
authors.lastname: De Raeve
authors.forename: Guerrino
authors.initials: G
authors.lastname: Meneguzzi
mesh_terms: D016110:Epidermolysis Bullosa Simplex / Q000235:genetics*; D005091:Exons; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D051190:Plectin; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D007381:Intermediate Filament Proteins; C495332:PLEC protein, human; D051190:Plectin