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
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.