A homozygous nonsense mutation in type XVII collagen gene (COL17A1) uncovers an alternatively spliced mRNA accounting for an unusually mild form of non-Herlitz junctional epidermolysis bullosa
L. Ruzzi et al., A homozygous nonsense mutation in type XVII collagen gene (COL17A1) uncovers an alternatively spliced mRNA accounting for an unusually mild form of non-Herlitz junctional epidermolysis bullosa, J INVES DER, 116(1), 2001, pp. 182-187
In this study we describe six Italian patients presenting an unusually mild
variant of non-Herlitz junctional epidermolysis bullosa associated with a
reduced expression of type XVII collagen. All patients are homozygous for a
novel nonsense mutation (R795X) within exon 33 of COL17A1 and show a commo
n haplotype, attesting propagation of an ancestral allele within the Italia
n population. Analysis of patients' COL17A1 transcripts showed the presence
of two mRNA species: a normal-sized mRNA carrying mutation R795X that unde
rgoes rapid decay, and a transcript generated by in-frame skipping of exon
33, Patients' keratinocytes were shown to synthesize minute amounts of type
XVII collagen, which appeared correctly localized along the cutaneous base
ment membrane. We therefore suggest that the exon 33-deleted COL17A1 splice
variant encodes for type XVII collagen molecules that maintain a functiona
l role and account for the mild phenotype of our patients.