1. ¹Centre for Blistering Skin Diseases, Department of Dermatology, Groningen University Hospital, Groningen, The Netherlands
2. ²Department of Dermatology, University of Oslo and Institute of Forensic Medicine, Oslo, Norway
3. ³Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands

Correspondence: Dr. Marcel F. Jonkman, Department of Dermatology, Groningen University Hospital, Hanzeplein 1, NL-9700 RB Groningen, the Netherlands. E-mail: m.f.jonkman@derm.azg.nl

Received 26 February 2001.

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.