Table 10.

Epidermolysis Bullosa Simplex: Mechanism of Disease Causation

Gene 1Special Consideration
CD151 Loss-of-function variants assoc w/AR inheritance
KLHL24 Gain-of-function & dominant-negative variants assoc w/AD inheritance.
  • 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
  • Dominant-negative missense variants assoc w/AD inheritance
  • Loss-of-function (typically functionally null alleles) variants that have been assoc w/AR inheritance
  • 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


Genes from Table 1 in alphabetic order

From: Epidermolysis Bullosa Simplex

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