title: A homozygous in-frame deletion in the collagenous domain of bullous pemphigoid antigen BP180 (type XVII collagen) causes generalized atrophic benign epidermolysis bullosa.
abstract: We report a missplicing event affecting the expression of bullous pemphigoid antigen BP180 (type XVII collagen) in a patient with generalized atrophic benign epidermolysis bullosa (GABEB). The segregation of the mutated allele in the family is consistent with the pathogenic role of the mutation. The homozygous mutation 2441-2A --> G disrupts a splice-site sequence in gene (BPAG2) for BP180 and results in an in-frame exon skipping within the collagenous ectodomain of the protein. The consequent deletion of 9 amino acids in the mutant BP180 is predicted to alter the structure of the homotrimer and is expected to exert a deleterious effect on stability of the protein that would account for the complete absence of immunoreactivity of the proband's skin to antibodies directed against BP180. These findings underscore the importance of structural integrity of the extracellular domain of BP180 for the stability of the protein.
authors.affiliation: U385 Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Chavanas
authors.forename: Y
authors.initials: Y
authors.lastname: Gache
authors.forename: G
authors.initials: G
authors.lastname: Tadini
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: J P
authors.initials: JP
authors.lastname: Ortonne
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
mesh_terms: D000328:Adult; D001324:Autoantigens / Q000737:chemistry* / Q000235:genetics*; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D016108:Epidermolysis Bullosa Dystrophica / Q000209:etiology*; D005260:Female; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D006720:Homozygote; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C486268:DST protein, human