title: Disruption of ERBB2IP is not associated with dystrophic epidermolysis bullosa in both father and son carrying a balanced 5;13 translocation.
abstract: Mutations in the type VII collagen gene (COL7A1) cause autosomal recessive and autosomal dominant inherited dystrophic epidermolysis bullosa (DEB). We report a family with three individuals who present blistering, scarring, hypo- and hyperpigmentation, and nail dystrophy suggestive for DEB. Whereas father and son carry a 5;13 translocation, the daughter shows a normal karyotype. Segregation analysis revealed that all affected family members inherited the same COL7A1 allele. Mutation analysis disclosed a heterozygous missense mutation, c.6227G > A (p.G2076D), in COL7A1 in all affected individuals. Delineation of the translocation breakpoints showed that the ERBB2IP (erbb2 interacting protein or Erbin) gene is disrupted in 5q13.1 and GPC6 in 13q32. GPC6 encodes glypican 6 belonging to a family of cell surface heparan sulfate proteoglycans. The binding partners of Erbin, BP230 (BPAG1) and the integrin beta4 subunit, both involved in hemidesmosome (HD) function, and the presence of Erbin in HD suggested that it plays a role in establishment and maintenance of cell-basement membrane adhesions. However, loss of function of one ERBB2IP copy or expression of a putative novel ERBB2IP fusion protein did not apparently modulate the DEB phenotype in both translocation patients. Nonetheless, one cannot yet exclude that ERBB2IP is a candidate for human blistering disorders such as epidermolysis bullosa.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Margarita
authors.initials: M
authors.lastname: Stefanova
authors.forename: Katrin
authors.initials: K
authors.lastname: Zemke
authors.forename: Boyan
authors.initials: B
authors.lastname: Dimitrov
authors.forename: Christina
authors.initials: C
authors.lastname: Has
authors.forename: Johannes S
authors.initials: JS
authors.lastname: Kern
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kutsche
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002882:Chromosomes, Human, Pair 13; D002895:Chromosomes, Human, Pair 5; D024143:Collagen Type VII / Q000235:genetics*; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics*; D005220:Fathers; D005260:Female; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D014178:Translocation, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D024143:Collagen Type VII; C413364:ERBIN protein, human; C120300:GPC6 protein, human; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans