Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non‐sense variant

Abstract

Background-Plectin, a large linker protein found in many tissues, acts to connect components of the cytoskeleton to each other. In the epidermis, plectin binds keratin intermediate filaments to hemidesmosomes. A deficiency of plectin in the skin leads to blister formation in the basal layer and the disease epidermolysis bullosa simplex (EBS).

Establishment and characterization of a canine keratinocyte organoid culture system

“…Similarly, organoids have the potential (after addition of respective growth factors) to differentiate into mature IFE structures. Because cell–cell adhesion molecules are expressed in IFE organoids at similar levels to control epidermis and, importantly, markers that play an important role in developing epidermolysis bullosa (such as KRT5 and KRT14) are overexpressed, the canine keratinocyte organoids are a potential model to investigate blistering diseases (such as pemphigus vulgaris and epidermolysis bullosa) …”

A nonsense variant in the KRT14 gene in a domestic shorthair cat with epidermolysis bullosa simplex

“…Epidermolysis bullosa (EB) is a group of hereditary diseases in humans and animals characterized by skin blistering owing to defects in structural proteins of the epidermis (Fine et al 2014;Medeiros & Riet-Correa 2015). EB is subdivided into four major types based on the level of split formation: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome, of which only the first three types have been described in domestic animals (Mauldin et al 2017). In humans, EBS, JEB and DEB are further classified into generalized and localized forms, a classification that has not been established for animals (Fine et al 2014;Medeiros & Riet-Correa 2015).…”

“…EBS is characterized by intraepithelial split formation and is associated with variants in the genes DSP (desmoplakin; human), DST (dystonin; humans), EXPH5 (exophilin 5; humans), JUP (junction plakoglobin; humans), KRT5 (keratin 5; humans, cattle), KRT14 (keratin 14; humans), PKP1 (plakophilin 1; humans, dogs), PLEC (plectin; humans, dogs) and TGM5 (transglutaminase 5; humans) (Medeiros & Riet-Correa 2015;Fine et al 2014;Mauldin et al 2017). While pathogenic variants in the DST, EXPH5, KRT5, KRT14 and PLEC genes evoke intrabasal split formation, variants in the remaining genes result in suprabasal separation (Fine et al 2014).…”

“…Genetic variants in KRT5 and KRT14 are the most frequent cause of EBS in humans (Coulombe et al 2009;Bolling et al 2011). In animals, EBS with intrabasal split formation has only been described in cattle and dogs (Medeiros & Riet-Correa 2015;Mauldin et al 2017). In cattle with a dominant form of EBS, a missense variant in the KRT5 gene has been identified (Ford et al 2005).…”

“…In cattle with a dominant form of EBS, a missense variant in the KRT5 gene has been identified (Ford et al 2005). In a litter of Eurasier dogs with recessive EBS, a nonsense variant in the PLEC gene encoding plectin was found (Mauldin et al 2017).…”