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

Laura Ruzzi, Hendri Pas, Patrizia Posteraro, Cinzia Mazzanti, Biagio Didona, Katsushi Owaribe, Guerrino Meneguzzi, Giovanna Zambruno, Daniele Castiglia, Marina D'alessio

Research output: Contribution to journalArticle

Abstract

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 common haplotype, attesting propagation of an ancestral allele within the Italian population. Analysis of patients' COL17A1 transcripts showed the presence of two mRNA species: a normal-sized mRNA carrying mutation R795X that undergoes 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 basement membrane. We therefore suggest that the exon 33-deleted COL17A1 splice variant encodes for type XVII collagen molecules that maintain a functional role and account for the mild phenotype of our patients.

Original languageEnglish
Pages (from-to)182-187
Number of pages6
JournalJournal of Investigative Dermatology
Volume116
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • Alternative splicing
  • COL17A1
  • Non-Herlitz junctional epidermolysis bullosa
  • Nonsense mutation
  • Recurrent mutation

ASJC Scopus subject areas

  • Dermatology

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