KRT13 and Hereditary Mucosal Leukokeratosis

This summary outlines the association between KRT13 and hereditary mucosal leukokeratosis, a condition traditionally recognized as white sponge nevus (WSN). Multiple studies from diverse populations have implicated heterozygous mutations in KRT13, strongly supporting its role in the pathogenesis of this autosomal dominant disorder (PMID:18992023). The condition is characterized by painless, thickened white plaques on the oral mucosa and may occasionally involve other mucosal sites. The clinical phenotype is consistent across reported families and emphasizes the importance of genetic testing in diagnosis.

Genetic evidence originates from several well‐documented case reports and family-based studies. In one Chinese family, a 32‑year‑old female patient along with her mother, younger sister, and daughter were shown to harbor causative variants in KRT13 (PMID:18992023). Another report from Saudi Arabia confirmed autosomal dominant inheritance based on familial testing, while Swedish families further demonstrated segregation of KRT13 variants with the disease phenotype (PMID:29047160). The consistency across these unrelated families strengthens the gene–disease association.

Segregation analysis across multiple reports shows that affected relatives in extended families consistently carry the pathogenic variants. One four‑generation study reported a total of 12 affected individuals, with at least 11 additional segregating relatives identified (PMID:28878914). This robust familial aggregation, with an aggregate count of approximately 16 additional affected relatives across independent studies, further substantiates the clinical relevance of the genetic findings.

The variant spectrum in KRT13 includes several heterozygous missense mutations. Notably, the recurrent variant c.332T>C (p.Leu111Pro) has been reported in multiple studies (PMID:25606422) and serves as a key diagnostic marker. This variant, along with others reported in KRT13, underscores the mutation hot‐spot areas that are critical for protein function. These findings support the utilization of targeted sequencing approaches in clinical diagnostic settings.

Functional studies have provided further insights into the pathogenic mechanism. Expression profiling and protein degradation analyses indicate that mutations in KRT13 lead to impaired keratin network formation and abnormal ubiquitin‐mediated proteolysis (PMID:25527207). Epigenetic silencing has also been described in related contexts, suggesting that both mutation and dysregulation of expression contribute to the phenotype. These experimental findings are concordant with the clinical observations and reinforce the causative role of KRT13 in WSN.

While the majority of evidence supports the association with hereditary mucosal leukokeratosis, one report also noted the occurrence of oral squamous cell carcinoma in a subset of patients with KRT13 mutations (PMID:28878914). This potential expansion of the phenotypic spectrum requires further investigation and does not detract from the strong genetic evidence in WSN. Overall, the convergence of case reports, segregation data, and functional assays provides a cohesive narrative of gene pathogenicity.

In conclusion, the strong genetic and experimental evidence linking KRT13 mutations to hereditary mucosal leukokeratosis supports its clinical utility in diagnosis and targeted genetic testing. Key take‑home: Testing for the recurrent c.332T>C (p.Leu111Pro) variant in KRT13 is a critical diagnostic aid for patients with white sponge nevus, enabling early intervention and family counseling.

References

• Oral diseases • 2009 • Two new mutations in the keratin 4 gene causing oral white sponge nevus in Chinese family PMID:18992023
• Cureus • 2022 • A Case Report on Familial White Sponge Nevus in Saudi Arabia PMID:36686092
• Orphanet journal of rare diseases • 2015 • Expression profiling of white sponge nevus by RNA sequencing revealed pathological pathways PMID:26062705
• Journal of oral pathology & medicine • 2018 • Mutations in the genes for keratin‑4 and keratin‑13 in Swedish patients with white sponge nevus PMID:29047160
• Meta gene • 2014 • Keratin 13 mutations associated with oral white sponge nevus in two Chinese families PMID:25606422
• Clinical case reports • 2017 • A novel keratin 13 variant in a four‑generation family with white sponge nevus PMID:28878914
• BMC cancer • 2014 • Epigenetic alterations of the keratin 13 gene in oral squamous cell carcinoma PMID:25527207

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