A novel mutation in the keratin 13 gene causing oral white sponge nevus

White sponge nevus (WSN) is an autosomal-dominantly inherited form of mucos al leukokeratosis. Defects in keratins, proteins that form the stress-beari ng cytoskeleton in epithelia, have been shown to cause several epithelial f ragility disorders. Recently, mutations in the genes encoding mucosal-speci fic keratins K4 and K13 were shown to be the underlying cause of WSN. We ha ve studied a large Scottish family with 19 persons affected by WSN in four generations. The K4 locus was excluded by genetic linkage analysis; however , genetic linkage consistent with a K13 defect was obtained. Subsequently, a heterozygous missense mutation 335A>G was detected in exon I of the KRT13 gene, predicting the amino acid change N112S in the IA domain of the K13 p olypeptide. The mutation was confirmed in affected family members and was e xcluded from 50 unaffected people by restriction enzyme analysis. These res ults confirm that mucosal keratin defects are the cause of WSN.