title: Mutations in the 180-kD bullous pemphigoid antigen (BPAG2), a hemidesmosomal transmembrane collagen (COL17A1), in generalized atrophic benign epidermolysis bullosa.
abstract: Junctional epidermolysis bullosa (JEB) is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Characteristic ultrastructural findings in JEB are abnormalities in the hemidesmosome-anchoring filament complexes. These focal attachment structures, which extend from the intracellular compartment of the basal keratinocytes to the underlying basement membrane, have been shown to be hypoplastic or rudimentary in different forms of JEB. Previously, in different JEB phenotypes, mutations have been found in the three genes for the anchoring filament component laminin 5 (LAMA3, LAMB3, and LAMC2) and in the gene for the hemidesmosome-associated integrin beta 4 subunit. Here, we describe the first mutations in the gene encoding the 180-kD bullous pemphigoid antigen (BPAG2), a transmembranous hemidesmosomal collagen, also known as type XVII collagen (COL17A1). The patient is affected with generalized atrophic benign epidermolysis bullosa (GABEB), a rare variant of JEB, and is a compound heterozygote for premature termination codons on both alleles. These novel findings emphasize the molecular heterogeneity of this group of genodermatoses, and attest to the importance of BPAG2 in maintaining adhesion between the epidermis and the dermis.
authors.affiliation: Department of Dermatology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: B
authors.initials: B
authors.lastname: Gatalica
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Owaribe
authors.forename: J R
authors.initials: JR
authors.lastname: McMillan
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000293:Adolescent; D000954:Antigens, Surface / Q000032:analysis; D001284:Atrophy; D001483:Base Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D003896:Desmosomes / Q000648:ultrastructure*; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D039161:Integrin alpha6beta4; D016023:Integrins / Q000032:analysis; D015603:Keratinocytes / Q000648:ultrastructure; D007797:Laminin / Q000032:analysis; D008297:Male; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation
chemical_list: D000954:Antigens, Surface; D018076:DNA, Complementary; D039161:Integrin alpha6beta4; D016023:Integrins; D007797:Laminin