Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands: Expansion of the mutation database and unusual phenotype-genotype correlations

Peter C. van den Akker*, Anthonie J. van Essen, Marian M. J. Kraak, Rowdy Meijer, Albertine Nijenhuis, Robert M. W. Hofstra, Hendri H. Pas, Hans Scheffer, Marcel F. Jonkman, G. Meijer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)

Abstract

Background: The current classification of recessive dystrophic epidermolysis bullosa (RDEB) comprises two major subtypes: 'severe generalized RDEB'(RDEB-sev gen) with early-onset, extensive, generalized blistering and scarring, complete absence of type VII Collagen, and bi-allelic COL7A1 null mutations; milder 'generalized other RDEB' (RDEB-O) with reduced-to-normal type VII Collagen expression, and non-null genotypes.

Objective: To search for previously unrecognized phenotype-genotype correlations in 33 Dutch RDEB families.

Methods: We analyzed extensive clinical follow-up data, available for all patients up to 19 years, detailed type VII Collagen immunostaining and genotypes, and correlated clinical phenotype to molecular phenotype and genotype.

Results: We identified 20 novel COL7A1 mutations. In 14 of 15 RDEB-sev gen patients type VII Collagen was completely absent, one had strongly reduced type VII Collagen, and all carried bi-allelic null mutations. Five of 11 RDEB-O patients developed pseudosyndactyly of the fingers preceded by skin atrophy and flexion contractures later in childhood and adolescence. All five had esophageal involvement and growth retardation. Type VII collagen immunostaining ranged from strongly reduced to slightly reduced in RDEB-O patients with pseudosyndactyly, whereas RDEB-O patients without pseudosyndactyly had slightly reduced to normal type VII Collagen staining. There was no difference in genotypes between both groups, although we unexpectedly found bi-allelic null mutations in two of five RDEB-O patients with pseudosyndactyly.

Conclusion: Pseudosyndactyly occurs in approximately half of RDEB-O patients when type VII Collagen is strongly reduced. The prognosis in RDEB cannot always be simply predicted from the COL7A1 genotype. (C) 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)9-18
Number of pages10
JournalJournal of dermatological science
Volume56
Issue number1
DOIs
Publication statusPublished - Oct-2009

Keywords

  • Recessive dystrophic epidermolysis bullosa
  • COL7A1
  • Type VII collagen
  • Phenotype-genotype correlations
  • Mechanobullous skin disease
  • VII COLLAGEN GENE
  • MESSENGER-RNA DECAY
  • EXONIC SPLICING ENHANCERS
  • REVERTANT MOSAICISM
  • ANCHORING FIBRILS
  • DISEASE SEVERITY
  • COL7A1 MUTATION
  • NONSENSE
  • DOMAIN
  • SKIN

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