Sabine Jägle, Hazem A. Juratli, Geoffroy Hickman, Kira Süssmuth, Maria C. Boente, Julia Kopp, Peter Kirchmeier, Andreas Zimmer, Rudolf Happle, Emmanuelle Bourrat, Henning Hamm, Judith Fischer
DOI: 10.2340/00015555-3753

Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho­genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known. This study analysed a cohort of 4 patients with linear porokeratosis and 3 patients with porokeratosis plantaris, palmaris et disseminata, and performed mutation analyses of DNA extracted from blood samples and skin biopsies. All of the study patients carried the heterozygous germline variant c.70+5G>A in the MVD gene. Loss of heterozygosity due to a second hit mutation was found in affected skin of 3 patients with linear porokeratosis and 2 patients with porokeratosis plantaris, palmaris et disseminata. These results suggest that porokeratosis plantaris, palmaris et disseminata shares the same pathogenetic mechanism as other porokeratosis subtypes and belongs to the phenotypic spectrum of MVD-associated porokeratosis.

The molecular cause of porokeratosis plantaris, palmaris et disseminata is unknown. This study found that, on a molecular level, porokeratosis plantaris, palmaris et disseminata is caused by a first mutation that is present in all cells of the body plus a second mutation found only in the skin lesions. The molecular mechanism for the development of porokeratosis plantaris, palmaris et disseminata is therefore the same as in other porokeratosis subtypes. Since the first mutation is present in all cells of the body, people with porokeratosis plantaris, palmaris et disseminata can pass on this mutation to their children, who are therefore at higher risk of also developing porokeratosis.