Keratin 4 regulates the development of human white sponge nevus

Abstract

Our study indicated the mutated KRT4 gene may play important roles in the pathogenesis of WSN.

White sponge nevus: A condition not always clinically suspected

“…The histopathological features of WSN include epithelial thickening, hyperparakeratosis, and vacuolization of the keratinocytes in the suprabasal layers. In addition, compact cytokeratin (CK) aggregates are visible in the upper epithelial layers, such as those found in epidermal disorders associated with cytokeratin defects . CK belong to a family of over 20 proteins that form the cytoskeleton of intermediate filaments of epithelial cells .…”

“…The microscopic features consist on oral hyperparakeratosis, acanthosis with intracellular edema, and eosinophilic deposition of tonofilaments of keratin around the nuclei of keratinocytes . Few cases of WSN have been reported in the English language literature so far, mostly as single case reports diagnosed clinically . We herein present four new cases of WSN diagnosed microscopically in a single oral pathology laboratory.…”

“…White sponge nevus (WSN) is a rare benign inherited disorder of autosomal‐dominant transmission that involves mutations in the cytokeratin 4 and cytokeratin 13 genes, which result in keratin instability and tonofilament aggregation, causing whitish lesions on nonkeratinized epithelial surfaces . Familial cases may occur, but they are uncommon, as a result of irregular penetrance of the trait …”

KRT4 suppresses oral squamous cell carcinoma development by reducing ATG4B-mediated autophagy

“…Several studies have revealed that KRT4 was downregulated in OSCC (Lallemant et al, 2009;Toruner et al, 2004;Ye et al, 2008). KRT4 belongs to the Type II keratin, which is specifically expressed with family member KRT13 in differentiated layers of the mucosal and esophageal epithelia (Zhang et al, 2018a). Mutations of these genes would lead to White Sponge Nevus (WSN) (Zhang et al, 2018a).…”

“…KRT4 belongs to the Type II keratin, which is specifically expressed with family member KRT13 in differentiated layers of the mucosal and esophageal epithelia (Zhang et al, 2018a). Mutations of these genes would lead to White Sponge Nevus (WSN) (Zhang et al, 2018a). A previous study has revealed that KRT4 serves as a tumor marker in esophageal squamous cell carcinoma (Takikita et al, 2011).…”