Truncated type XVII collagen expression in a patient with non-Herlitz junctional epidermolysis bullosa caused by a homozygous splice-site mutation

Citation
Mr. Van Leusden et al., Truncated type XVII collagen expression in a patient with non-Herlitz junctional epidermolysis bullosa caused by a homozygous splice-site mutation, LAB INV, 81(6), 2001, pp. 887-894
Citations number
45
Categorie Soggetti
Medical Research General Topics
Journal title
LABORATORY INVESTIGATION
ISSN journal
00236837 → ACNP
Volume
81
Issue
6
Year of publication
2001
Pages
887 - 894
Database
ISI
SICI code
0023-6837(200106)81:6<887:TTXCEI>2.0.ZU;2-#
Abstract
Type XVII collagen (180-kDa bullous pemphigoid antigen) is a structural com ponent of hemidesmosomes. Mutations in the type XVII collagen gene (COL 17A 1) have been established to be the molecular basis of non-Herlitz junctiona l epidermolysis bullosa (JEB-nH), an inherited skin blistering disorder. He re we report for the first time truncated type XVII collagen expression, ca used 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 an d sequencing of cDNA derived from mRNA from the patient's cultured keratino cytes, we provide evidence of cryptic splicing and exon skipping, most abun dantly of exon 52. JEB-nH patients with COL17A1 splice-site mutations resul ting in an exon skip often have no immunologically detectable type XVII col lagen. However, in our patient with the generalized atrophic benign epiderm olysis bullosa subtype, a small amount of type XVII collagen was detectable in the skin, and immunoblotting of cultured keratinocytes revealed that th e 180-kDa protein was 10 kDa shorter. We hypothesize that the function of t his truncated type XVII collagen polypeptide, which is expressed at low lev els, is impaired, explaining the JEB-nH phenotype.