Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility
Pierre A. Coulombe, … , Michelle L. Kerns, Elaine Fuchs
Pierre A. Coulombe, … , Michelle L. Kerns, Elaine Fuchs
Published July 1, 2009
Citation Information: J Clin Invest. 2009;119(7):1784-1793. https://doi.org/10.1172/JCI38177.
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Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility

Abstract

Epidermolysis bullosa (EB) simplex is a rare genetic condition typified by superficial bullous lesions that result from frictional trauma to the skin. Most cases are due to dominantly acting mutations in either keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins tasked with forming a pancytoplasmic network of 10-nm filaments in basal keratinocytes of the epidermis and in other stratified epithelia. Defects in K5/K14 filament network architecture cause basal keratinocytes to become fragile and account for their trauma-induced rupture. Here we review how laboratory investigations centered on keratin biology have deepened our understanding of the etiology and pathophysiology of EB simplex and revealed novel avenues for its therapy.

Authors

Pierre A. Coulombe, Michelle L. Kerns, Elaine Fuchs

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Figure 4

Distribution of mutations in K5 and K14 as a function of disease variant in EB simplex.

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Distribution of mutations in K5 and K14 as a function of disease variant...
(A) Histogram depicting the number of cases of mutations in K5 and K14 as a function of EB simplex variant. The category “Others” corresponds to the aggregate of most other variants of the disease, excluding EBS-MD (see Table 1). (B) Distribution of mutations as a function of position within K5 and K14 and clinical variant of the disease. See main text and Figure 1 for information about keratin protein secondary structure. Each entry consists of three numbers: the top one is the total number of mutations; the bottom left number is the subset of these mutations that affect K5; and the bottom right number is the subset of these mutations that affect K14. “None” indicates the absence of mutations for this region of K5 or K14. Red numbers convey the occurrence of a bias toward either K5 or K14. The data are derived from ref. 11. EBS-AR, EB simplex autosomal recessive; EBS-gen, EBS-generalized; EBS-local, EBS-localized; HIM, helix initiation motif; HTM, helix termination motif.