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The inversa type of recessive dystrophic epidermolysis bullosa is caused by specific arginine and glycine substitutions in type VII collagen
  1. Peter C van den Akker1,
  2. Jemima E Mellerio2,3,
  3. Anna E Martinez3,
  4. Lu Liu4,
  5. Rowdy Meijer5,
  6. Patricia J C Dopping-Hepenstal4,
  7. Anthonie J van Essen1,
  8. Hans Scheffer5,
  9. Robert M W Hofstra1,
  10. John A McGrath6,
  11. Marcel F Jonkman7
  1. 1Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK
  3. 3Department of Dermatology, Great Ormond Street Hospital NHS Trust, London, UK
  4. 4The Robin Eady National Diagnostic Epidermolysis Bullosa Laboratory, GSTS Pathology, St John's Institute of Dermatology, St Thomas' Hospital, London, UK
  5. 5Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  6. 6St John's Institute of Dermatology, King's College London (Guy's Campus) and Guy's and St Thomas' NHS Foundation Trust, London, UK
  7. 7Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Peter C van den Akker, Department of Genetics, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands; p.c.van.den.akker{at}medgen.umcg.nl

Abstract

Background The inversa type of recessive dystrophic epidermolysis bullosa (RDEB-I) is a rare variant of dystrophic epidermolysis bullosa, characterised by blistering in the body flexures, trunk, and mucosa. The cause of this specific distribution is unknown. So far, 20 COL7A1 genotypes have been described in RDEB-I and genotype–phenotype correlations have not been studied extensively. The aim of the study was to gain more insight into the pathophysiology of this intriguing RDEB-I phenotype.

Methods Twenty Dutch and British RDEB-I patients, and full genotypes in 18 of them, were identified. The literature on RDEB-I genotypes was reviewed and an extensive genotype–phenotype correlation study for RDEB-I was conducted.

Results All 20 patients had generalised blistering at birth and during early infancy. In most patients, the age of transition from generalised to inversa distribution was before the age of 4 years. A spectrum of disease severity, ranging from the mildest ‘mucosal only’ phenotype to the severest phenotype with limited acral involvement, was noted. The 29 genotypes of these RDEB-I patients and those reported in the literature revealed that RDEB-I is associated with specific recessive arginine and glycine substitutions in the triple helix domain of type VII collagen.

Discussion and conclusion Why these specific arginine and glycine substitutions cause the inversa distribution remains unknown. It was not possible to identify clear differences in location and nature of substituting amino acids between these mutations and missense mutations causing other RDEB phenotypes. It is hypothesised that the higher skin temperature in the affected areas plays an important role in the pathophysiology of RDEB-I.

  • Recessive dystrophic epidermolysis bullosa
  • inversa type
  • genotype–phenotype correlations
  • type VII collagen
  • COL7A1
  • dermatology
  • clinical genetics

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Footnotes

  • Funding This study was supported by The Netherlands Organization for Health Research and Development (ZonMw) grant 92003541. JEM and JAM acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the local ethical boards (IRBs).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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