Jägle Sabine, Juratli Hazem A, Hickman Geoffroy, Süssmuth Kira, Boente Maria C, Kopp Julia, Kirchmeier Peter, Zimmer Andreas, Happle Rudolf, Bourrat Emmanuelle, Hamm Henning, Fischer Judith
Institute of Human Genetics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, DE-79106 Freiburg, Germany.
Acta Derm Venereol. 2021 Feb 16;101(2):adv00397. 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 patho-genetic 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.
汗孔角化症是一组异质性的角化障碍性疾病。对于线状汗孔角化症和播散性浅表性光化性汗孔角化症，已证实甲羟戊酸途径基因中的杂合致病性种系变异以及受影响皮肤中存在的合子后二次打击突变是病变发生发展的致病机制。然而，掌跖播散性汗孔角化症发生发展的分子机制尚不清楚。本研究分析了4例线状汗孔角化症患者和3例掌跖播散性汗孔角化症患者的队列，并对从血液样本和皮肤活检组织中提取的DNA进行了突变分析。所有研究患者均携带MVD基因中的杂合种系变异c.70+5G>A。在3例线状汗孔角化症患者和2例掌跖播散性汗孔角化症患者的受影响皮肤中发现了由于二次打击突变导致的杂合性缺失。这些结果表明，掌跖播散性汗孔角化症与其他汗孔角化症亚型具有相同的致病机制，属于MVD相关汗孔角化症的表型谱。
