Disruption of ERBB2IP Is not Associated with Dystrophic Epidermolysis Bullosa in Both Father and Son Carrying a Balanced 5;13 Translocation

• Published in: Journal of investigative dermatology Vol. 125; no. 4; pp. 700 - 704
• Main Authors: Stefanova, Margarita, Zemke, Katrin, Dimitrov, Boyan, Has, Christina, Kern, Johannes S., Bruckner-Tuderman, Leena, Kutsche, Kerstin
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-10-2005; Nature Publishing; Elsevier Limited
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Biological and medical sciences; Bullous diseases of the skin; Carrier Proteins - genetics; Child; Chromosome aberrations; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 5; Collagen Type VII - genetics; Dermatology; disrupted gene; dystrophic epidermolysis bullosa; Epidermolysis Bullosa Dystrophica - genetics; ERBB2IP; Fathers; Female; Glypicans; GPC6; Heparan Sulfate Proteoglycans - genetics; Humans; Male; Medical genetics; Medical sciences; Middle Aged; Nuclear Family; translocation breakpoint; Translocation, Genetic; ERBB2IP; disrupted gene; GPC6; translocation breakpoint; dystrophic epidermolysis bullosa; Chromosomal aberration; Bullous dermatosis; Breakpoint; Skin disease; Dermatology; Family study; Genetic disease; disrupted gene/dystrophic epidermolysis bullosa/ERB6B2IP/GPC6/translocation breakpoint; Gene; Cytogenetics; Abnormal chromosome; Genetics; Father; Dystrophic epidermolysis bullosa; Chromosome translocation
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2005.23875.x

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 β4 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.