Keratin 13 point mutation underlies the hereditary mucosal epithelial disorder white sponge nevus.
Although pathogenic keratin mutations have been well characterized in inherited epidermal disorders, analogous defects in keratins expressed in non-epidermal epithelia have yet to be described. White sponge nevus (WSN) is a rare autosomal dominant disorder of non-cornifying squamous epithelial differentiation that presents clinically as bilateral white, soft, thick plaques of the oral mucosa. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved. Histopathological features, including epithelial thickening, parakeratosis, extensive vacuolization of the suprabasal keratinocytes and compact aggregates of keratin intermediate filaments (KIF) in the upper spinous layers, resemble those found in epidermal disorders due to keratin defects. We analysed a multigenerational family with WSN and found cosegregation of the disease with the keratin gene cluster on chromosome 17. We identified a missense mutation in one allele of keratin 13 that leads to proline substitution for a conserved leucine. The mutation occurred within the conserved 1A region of the helical rod domain, which is critical for KIF stability and is the site of most pathogenic keratin mutations. This mutation enlarges the spectrum of keratins with disease-causing defects to include mucosally expressed keratin 13, and extends the known keratin diseases to disorders of non-cornifying stratified squamous epithelia.
D000595:Amino Acid Sequence; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D004848:Epithelium; D005260:Female; D008040:Genetic Linkage; D006222:Hamartoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000235:genetics*; D007972:Leukoplakia, Oral / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000737:chemistry*; D005810:Multigene Family; D010375:Pedigree; D017354:Point Mutation
D007633:Keratins