Zhang et al. (2004) studied 2 unrelated Chinese families segregating autosomal dominant punctate palmoplantar keratoderma. In the first family, which had 9 affected individuals in 4 generations, the proband was a 50-year-old woman who first noticed symptoms at ... Zhang et al. (2004) studied 2 unrelated Chinese families segregating autosomal dominant punctate palmoplantar keratoderma. In the first family, which had 9 affected individuals in 4 generations, the proband was a 50-year-old woman who first noticed symptoms at 15 years of age. In the second family there were 5 affected individuals over 3 generations; the proband was a 42-year-old man who at 14 years of age developed several pinhead-size hyperkeratotic papules, first on the soles, then on the palms, which were barely noticeable. Skin biopsy of the lesions showed notable hyperkeratosis with large, wide, and cup-like keratin plugs. At the edge of the lesion, instead of small spikes, there were projections of keratin plugs. The depth of the stratum granulosum was increased, the stratum spinosum was thickened, and there were prominent extensions of epithelial pegs. The proliferation of the epidermis and upward extension of the dermal papillae resulted in papillomatous hyperplasia.
In 4 affected and 2 unaffected members of a 4-generation Chinese family with autosomal dominant punctate palmoplantar keratoderma mapping to chromosome 8q24, previously studied by Zhang et al. (2004), Guo et al. (2012) performed exome capture and sequencing ... In 4 affected and 2 unaffected members of a 4-generation Chinese family with autosomal dominant punctate palmoplantar keratoderma mapping to chromosome 8q24, previously studied by Zhang et al. (2004), Guo et al. (2012) performed exome capture and sequencing and identified a heterozygous missense mutation in the COL14A1 gene (P1502L; 120324.0001) that was present in the 4 affected but not the 2 unaffected family members. Sanger sequencing revealed that the mutation was present in 4 additional affected family members, as well as 2 unaffected family members, a 15-year-old boy and his uncle. The mutation was not found in 676 unrelated ethnically and geographically matched controls, or in 718 unrelated ethnically and geographically matched patients with other diseases. Guo et al. (2012) suggested that COL14A1 might be a causal gene for PPKP, noting that the unaffected 15-year-old boy with the mutation was at the lower limit for average age at onset of disease in this family and might yet develop symptoms. Sequencing of the coding exons and intron-exon boundaries of COL14A1 in a second 3-generation Chinese family with PPKP mapping to 8q24, also previously studied by Zhang et al. (2004), did not reveal any potential pathogenic mutations.