Keratosis Palmoplantaris Striata Iii

A number sign (#) is used with this entry because of evidence that keratosis palmoplantaris striata III (PPKS3) is caused by heterozygous mutation in the keratin-1 gene (KRT1; 139350) on chromosome 12q13.

For a discussion of genetic heterogeneity of the striate form of palmoplantar keratoderma, see PPKS1 (148700).

Clinical Features

Whittock et al. (2002) studied a 4-generation family of British descent with striate palmoplantar keratoderma. Autosomal dominant inheritance was demonstrated. Affected individuals presented during early childhood with PPKS on the palms and more diffuse changes on the soles. There was no involvement of nonpalmoplantar skin, and both hair and nails were normal. Ultrastructural studies showed that intermediate filaments of suprabasal keratinocytes were finer than those of the basal layer. In addition, desmosome numbers were normal, but their inner plaques and midline structures were attenuated.

Mapping

In a 4-generation family with PPKS, Whittock et al. (2002) observed linkage to chromosome 12q using marker D12S368, with a maximum 2-point lod score of 3.496 at a recombination fraction of 0.

Molecular Genetics

By direct sequencing, Whittock et al. (2002) found a frameshift mutation in exon 9 (1628delG; 139350.0012) of the KRT1 gene that led to the partial loss of the glycine loop motif in the V2 domain and the gain of a novel 70-amino acid peptide. Using expression studies, Whittock et al. (2002) showed that the V2 domain is essential for normal function of keratin intermediate filaments. Whittock et al. (2002) noted that although the molecular defect in this family was similar to a KRT1 mutation causing ichthyosis hystrix (139350.0013), the changes in the keratin intermediate filaments were very different.