Table 10.

Epidermolysis Bullosa Simplex: Mechanism of Disease Causation

Gene 1Special Consideration
CD151 Loss-of-function variants assoc w/AR inheritance
DST
EXPH5
KLHL24 Gain-of-function & dominant-negative variants assoc w/AD inheritance.
KRT5
  • Dominant-negative missense variants assoc w/AD inheritance. The mechanism of disease is dependent on the variant, but often results in protein that prevents proper assoc w/the protein partner (e.g., keratin 5, keratin 14) & assembly of those assoc dimers into bundles & fibers.
  • Loss-of-function (typically functionally null alleles) variants assoc w/AR inheritance
KRT14
  • Dominant-negative missense variants assoc w/AD inheritance
  • Loss-of-function (typically functionally null alleles) variants that have been assoc w/AR inheritance
PLEC
  • The missense variant c.5998C>T identified in the AD subtype previously known as EBS-Ogna is presumed to be dominant negative [Koss-Harnes et al 2002].
  • Loss-of-function variants assoc w/AR subtypes incl EBS, intermediate w/PLEC pathogenic variants; EBS, intermediate w/muscular dystrophy; & EBS, severe w/ pyloric atresia

AD = autosomal dominant; AR = autosomal recessive; EBS = epidermolysis bullosa simplex

1.

Genes from Table 1 in alphabetic order

From: Epidermolysis Bullosa Simplex

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.