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Selected Heritable Skin Diseases of Domesticated Animals
Published in John P. Sundberg, Handbook of Mouse Mutations with Skin and Hair Abnormalities, 2020
Robert W. Dunstan, Robert A. Kennis
Comments — Although some clinical (absence of erythroderma and blistering) and ultrastructural (absence of perinuclear tonofilament shells) features distinguish the canine from the human disease, there are sufficient similarities to characterize the canine disease as an epidermolytic ichthyosis.4 In humans, three forms of epidermolytic ichthyoses are recognized: bullous ichthyotic erythroderma of Brocq, ichthyosis bullosa of Siemens, and ichthyosis hystrix of Curth-Macklin.4,5 In addition, forms of epidermolytic epidermal nevi have been recognized. Whether the canine disease can be categorized as one of these conditions remains to be defined. Recent studies have shown that human epidermolytic hyperkeratosis is associated with point mutations in the K1 and K10 genes. The mutation in the K10 gene is in the exact same arginine residue as the corresponding K14 mutation reported for human epidermolysis bullosa simplex.5–7 A fascinating investigation would be to determine if the same point mutations occur in canine epidermolytic ichthyosis.
Genodermatoses affecting the nail
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
The most common and mildest form of epidermolysis bullosa simplex is the Weber–Cockayne type (EBSWC; OMIM 131800) where blistering is limited to the hands and feet. Blisters are not present at birth, but develop later after an identifiable traumatic event. Secondary infections of blistering lesions on the feet are the most common complication. Nail changes are not a common feature, but periungual blisters and erosions may occasionally be seen. The Köbner type (EBS-K; OMIM 131900) manifests after birth with generalized, but relatively mild blistering also affecting hands and feet. The Dowling-Meara form (EBS-DM; OMIM 131760) is the most severe simplex subtype presenting with extensive grouped blistering, called “herpetiform” pattern. It is already present at birth with erosions and areas of denuded skin. Serous and hemorrhagic blisters develop on the entire skin, but most frequently on palms and soles, around the mouth, on the trunk, and neck. Oral mucosal involvement, progressive palmoplantar keratosis, and nail dystrophies are common. Usually the lesions heal without scarring; however, inflammation especially of hemorrhagic blisters may be followed by milia formation. EBS-DM with extensive involvement may be fatal in the neonatal period. Ultrastructural examination of skin biopsies shows characteristic clumps of keratin intermediate filaments in the cytoplasm of basal keratinocytes. These three EBS forms are due to keratin 5 and 14 mutations. EBS with mottled pigmentation is another rare subtype that may be associated with punctate palmar and plantar keratoses.114 Blistering is usually more pronounced in childhood. Nail changes may develop in later age. Bart's syndrome (OMIM 132000) is also thought to be an EBS with predominant blistering in the neonatal phase and later nail dystrophy.115 Further rare simplex types are due to mutations of the genes encoding plectin, the 230-kDa bullous pemphigoid antigen, β4 integrin, plakophilin-1, desmoplakin,116 plakoglobin, transglutaminase 5, and exophilin-5.117
Current developments in gene therapy for epidermolysis bullosa
Published in Expert Opinion on Biological Therapy, 2022
Thomas Kocher, Igor Petkovic, Johannes Bischof, Ulrich Koller
In recent years, gene therapies for genodermatoses have steadily become the focus of research. Several therapeutic strategies, based on RNA/DNA repair or substitution, are already at both preclinical and clinical stage (Figure 1). The monogenetic skin disease epidermolysis bullosa (EB) represents a strong gene therapy target, as pathogenic mutations in at least 16 unique genes, which are crucial for skin integrity, result in severe phenotypes [1]. EB is characterized by the formation of extended blisters and lesions on the skin and mucous membranes upon minimal mechanical trauma. Clinical and genetic aspects, genotype–phenotype correlations as well as disease-modifying factors of EB were thoroughly reviewed by Has and colleagues [1]. With ~500,000 people affected worldwide, EB is a rare and very heterogeneous skin disease, which can be divided into four major subtypes. Mutations within keratin 5, 14 and plectin lead to epidermolysis bullosa simplex (EBS), associated with intraepidermal blistering, whereas junctional EB (JEB) is caused by mutations in genes coding for laminin-332, type XVII collagen (C17) and integrin-α6β4. This form of EB is characterized by blistering within the lamina lucida of the basement membrane. Mutations within COL7A1, encoding type VII collagen (C7), are responsible for a particularly severe form of EB, dystrophic EB (DEB), while Kindler syndrome is caused by mutations within the KIND1 gene [1,2].
Gut commensal derived-valeric acid protects against radiation injuries
Published in Gut Microbes, 2020
Yuan Li, Jiali Dong, Huiwen Xiao, Shuqin Zhang, Bin Wang, Ming Cui, Saijun Fan
Keratins (KRTs) have yet been discovered consist of more than 20 members. A major role fulfilled by KRTs is to protect epithelial cells from mechanical and non-mechanical stresses. Additional functions of KRTs manifests including the regulation of cell signaling and stress responses.14,15 Dysfunction of KRT may cause various diseases. For example, epidermolysis bullosa simplex (EBS) is related to the mutation of KRT5 and KRT14.16 KRT8/KRT18 variants could be a risk factor for liver fibrosis progression.17 In addition, diffuse expression of KRT7 and KRT19 in the end-stage kidney could increase the risk of tumor development.18 Importantly, clinical and laboratory researches have demonstrated the significant role for KRTs in the protection of the epithelial integrity in the small intestine,19,20 and the down-regulation of KRT1 is correlated with the progression of inflammatory bowel disease (IBD).21 Our previous studies have shown that radiation could cause intestinal injury, covering elevated levels of inflammation and the destruction of intestinal integrity. However, whether KRT1 contributes to radioprotection remains an enigma.