Porokeratosis 9, Multiple Types

A number sign (#) is used with this entry because of evidence that multiple types of porokeratosis (POROK9) are caused by heterozygous mutation in the FDPS gene (134629) gene on chromosome 1q22.

Description

Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial.

Mutations in the FDPS gene have been found to cause multiple types of porokeratosis, which have been described as disseminated superficial actinic porokeratosis (DSAP) and nonactinic disseminated superficial porokeratosis (DSP).

For a discussion of genetic heterogeneity of porokeratosis, see 174800.

Molecular Genetics

Zhang et al. (2015) screened 12 isoprenoid genes in 134 Chinese probands with porokeratosis and identified 4 mutations in the FDPS gene in 4 probands, including 2 large deletions in 2 of them (see, e.g., 134629.0001-134629.0003). The mutations segregated with disease in all pedigrees for which DNA was available, and were not found in 270 controls. All 4 patients exhibited more than 500 lesions, with diameters ranging from 1 mm to 1 cm; the lesions were of the DSAP and/or nonactinic DSP subtypes. Zhang et al. (2015) noted that even within families, affected individuals carrying the same mutation showed varying degrees of severity. All examined lesional tissue showed cornoid lamella, a histologic hallmark of porokeratosis with vertical columns of parakeratosis overlying an area of hypogranulosis with dyskeratotic cells.