title: A novel autosomal partially dominant mutation designated G476D in the keratin 5 gene causing epidermolysis bullosa simplex Weber-Cockayne type: a family study with a genetic twist.
abstract: Epidermolysis bullosa simplex Weber-Cockayne type (EBS-WC) is a genetically inherited skin disease characterized by blistering restricted to the palms and soles. Its inheritance in nearly all kindreds is caused by a dominant-negative mutation in either KRT5 or KRT14, the genes encoding keratin 5 and keratin 14 proteins, respectively. Rarely, recessive mutations have also been found. We described a family with EBS-WC caused by a novel autosomal dominant mutation (G476D) in the keratin 5 gene. One family member was first seen with mucosal erosions and generalized blisters localized on the anogenital area, trunk, face and sites of mechanical trauma. Molecular analysis in this patient showed the presence of an additional mutation, an autosomal recessive (G183E) one, in the same gene. This observation suggests an additional effect of a recessively inherited mutation modulating the phenotypic expression of EBS caused by a partially dominant mutation and is important for accurate genetic counseling.
authors.affiliation: Department of Dermatology, Medical University of Warsaw, Warsaw, Poland. ckowalew@amwaw.edu.pl
authors.forename: Cezary
authors.initials: C
authors.lastname: Kowalewski
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wozniak
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawano
authors.forename: Weronika
authors.initials: W
authors.lastname: Szczecinska
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yasumoto
authors.forename: Robert A
authors.initials: RA
authors.lastname: Schwartz
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001216:Asparagine / Q000378:metabolism*; D001706:Biopsy; D004252:DNA Mutational Analysis; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics* / Q000473:pathology / Q000601:surgery / Q000648:ultrastructure; D005091:Exons; D005220:Fathers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000235:genetics*; D008297:Male; D010375:Pedigree
chemical_list: D053555:Keratin-5; D001216:Asparagine