Keratin 13 mutations associated with oral white sponge nevus in two Chinese families

Abstract

White sponge nevus (WSN) is an autosomal dominant hereditary disease. Keratin 4 (KRT4) and Keratin 13 (KRT13) gene mutations were involved in the WSN. We recruited two WSN Chinese families, and oral lesion biopsy with hematoxylin and eosin staining showed that patients had significant pathological characteristics. The mutations of KRT4 and KRT13 gene were detected by PCR and direct sequencing. The multiple alignments of KRT13 from 23 diverse species homology analyses were performed by the ClustalW program. The KRT13 expression was measured by Real-Time RT-PCR and Western blot analysis. Sequencing analysis revealed two mutations of KRT13 gene: one mutation was 332T>C and amino acid change was Leu111Pro. Another mutation was 340C>T and amino acid change was Arg114Cys. The sequence of KRT13 was highly conserved. Real-Time RT-PCR and Western blot analysis results show that KRT13 expression level is lower in patient but keep almost no change in mRNA level. When cells were treated with MG132, KRT13 protein level was increased and kept almost the same in normal and patient cells. We identified two heritable mutations in the KRT13 gene, which were associated with the development of WSN. The abnormal degradation of KRT13 protein of WSN may probably associate with the abnormal ubiquitination process.

Mutations in the genes for keratin‐4 and keratin‐13 in Swedish patients with white sponge nevus

“…With regard to the KRT13 gene, all the heterozygous missense mutations that have been reported are localised to the helix‐initiation motif of the alpha‐helical domain 1A, that is L119P, L115P and M108T, N112S, L111P, R114H and R114C . We found the same mutation as reported by Rugg et al in the KRT13 gene in the genomes of Family 1.…”

Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone

“…KRT13 expression is regulated by calcium, nuclear receptor ligands, estradiol, and selective estrogen receptor modulators [ 24 , 26 ]. KRT13 mutations are associated with the development of White Sponge Nevus, a condition characterized by thick white oral lesions [ 27 ]. Gradual loss of KRT13 expression in oral mucosa is linked to dysplastic transformation and squamous cell carcinoma [ 28 ].…”

Expression profiling of white sponge nevus by RNA sequencing revealed pathological pathways

“…UBC is a protein-coding gene that encodes a ubiquitin protein that exists either covalently attached to another protein or free (unanchored). Our previous study found that the abnormal degradation of the KRT13 protein in WSN patients contributed to an abnormal ubiquitination process [ 6 ]. Therefore, a key target for the treatment of WSN is to prevent the degradation of the KRT13 protein.…”

“…To develop better therapeutic strategies for WSN, it is important to understand the consequences of the associated genetic mutations and molecular changes. To date, many WSN cases have been reported around the world, including China [ 6 – 8 ], Italy [ 9 – 11 ], Japan [ 12 , 13 ], the UK [ 14 , 15 ], Spain [ 16 ], Scotland [ 17 ], Iran [ 18 ], Brazil [ 19 ], and Turkey [ 20 ]. However, the exact pathogenic mechanism behind WSN remains unclear.…”