title: Truncated typeXVII collagen expression in a patient with non-herlitz junctional epidermolysis bullosa caused by a homozygous splice-site mutation.
abstract: Type XVII collagen (180-kDa bullous pemphigoid antigen) is a structural component of hemidesmosomes. Mutations in the type XVII collagen gene (COL17A1) have been established to be the molecular basis of non-Herlitz junctional epidermolysis bullosa (JEB-nH), an inherited skin blistering disorder. Here we report for the first time truncated type XVII collagen expression, caused by homozygosity for a COL17A1 donor splice-site mutation (4261+1 g --> c), which was identified by PCR amplification on genomic DNA. By RT-PCR and sequencing of cDNA derived from mRNA from the patient's cultured keratinocytes, we provide evidence of cryptic splicing and exon skipping, most abundantly of exon 52. JEB-nH patients with COL17A1 splice-site mutations resulting in an exon skip often have no immunologically detectable type XVII collagen. However, in our patient with the generalized atrophic benign epidermolysis bullosa subtype, a small amount of type XVII collagen was detectable in the skin, and immunoblotting of cultured keratinocytes revealed that the 180-kDa protein was 10 kDa shorter. We hypothesize that the function of this truncated type XVII collagen polypeptide, which is expressed at low levels, is impaired, explaining the JEB-nH phenotype.
authors.affiliation: Centre for Blistering Skin Diseases, Department of Dermatology, Groningen University Hospital, Groningen, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: van Leusden
authors.forename: H H
authors.initials: HH
authors.lastname: Pas
authors.forename: T
authors.initials: T
authors.lastname: Gedde-Dahl
authors.forename: A
authors.initials: A
authors.lastname: Sonnenberg
authors.forename: M F
authors.initials: MF
authors.lastname: Jonkman
mesh_terms: D000368:Aged; D001483:Base Sequence / Q000235:genetics; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D004274:DNA, Recombinant; D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant; D010446:Peptide Fragments; D012333:RNA, Messenger; D003094:Collagen