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Epidermolysis bullosa
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Kindler syndrome is autosomal recessively inherited. It presents with blistering at birth or infancy. Blisters are generalized, usually subsiding in late childhood, giving rise to poikiloderma. Other features include photosensitivity, dystrophic nails, webbing of toes, gingival hyperplasia, periodontal disease, and rarely presents with complications such as esophagitis, esophageal strictures, colitis, urethral stricture, and ectropion requiring emergency management [5]. SCC can develop after the age of 30 years; hence, early and regular surveillance is important.
Photoexacerbated Dermatoses
Published in Henry W. Lim, Nicholas A. Soter, Clinical Photomedicine, 2018
Kindler syndrome (47) is characterized by photosensitivity, the formation of acral bullae in infancy and early childhood, generalized poikiloderma, diffuse cutaneous atrophy, photosensitivity, acral hyperkeratosis, webbing of the fingers and toes, nail dystrophy, and oral mucosal lesions. The photosensitivity is manifested by facial erythema after minimal sun exposure, blister formation in the summer, and susceptibility to severe sunburn. The action spectrum of the photosensitivity is unknown. An autosomal recessive mode of inheritance is believed to be most likely.
Suspended cell lines for inactivated virus vaccine production
Published in Expert Review of Vaccines, 2023
Jiayou Zhang, Zhenyu Qiu, Siya Wang, Zhenbin Liu, Ziling Qiao, Jiamin Wang, Kai Duan, Xuanxuan Nian, Zhongren Ma, Xiaoming Yang
Talin is the most characteristic binding protein linking integrins to actin and is a major component of focal adhesions (FAs). Talin has two subtypes, namely talin-1 and talin-2. Talin-1 gene knockout cell lines were established in fibroblasts, and it was found that they could not activate their integrins nor bind to the fibrin in ECM, thus leading to a significant decline in cell adhesion [96]. Other studies have confirmed the role of talin-1 in carcinogenesis and provided a new therapeutic target for the treatment of hepatocellular carcinoma (HCC). Furthermore, talin-1 may promote cell adhesion by regulating the epithelial-mesenchymal transition (EMT) process [97]. Studies have also shown that T cells and T cell exocrines lacking talin-2 show reduced binding with integrin ligands ICAM-1 and MAdCAM-1 [113], demonstrating that knockdown of the talin-2 gene can reduce cell adhesion. Kindlins, which contain three members (Kindlin-1, Kindlin-2, and Kindlin-3), are key cell-ECM adhesion proteins and key activators of integrins. Kindlin-2, also known as mig-2, can directly bind to the β1- and β3-integrin tail [98]. Studies have shown that knockdown of the Kindlin-2 gene can prevent the activation of integrins, thus significantly affecting the adhesion ability of cells [99]. Additionally, deficiencies in Kindlin-1 and Kindlin-3 can lead to diseases. For example, Kindlin-1 deficiency causes skin weakness and blistering (called Kindler syndrome), and Kindlin-3 deficiency causes hemorrhagic disease and immune deficiency.
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].
Emerging drugs for the treatment of epidermolysis bullosa
Published in Expert Opinion on Emerging Drugs, 2020
Matthias Titeux, Mathilde Bonnet des Claustres, Araksya Izmiryan, Helene Ragot, Alain Hovnanian
KEB formerly known as Kindler syndrome has recently been classified as new subtype of EB [1]. This form is caused by recessive mutations in the FERMT1 gene coding for kindlin, a protein that functions in making up focal contact points of basal keratinocytes. The cleavage levels are multiple and can occur within keratinocytes, in the lamina densa and below the lamina densa, and are often associated with duplication of the basement membrane [11]. Patients present with epidermal skin fragility and blistering, photosensitivity and progressive poikiloderma, marked skin atrophy and periodontal disease.