Wertheim-Tysarowska Katarzyna, Gos Monika, Niepokój Katarzyna, Kowalewski Cezary
Zakład Genetyki Medycznej, Instytut Matki I Dziecka, ul. Kasprzaka 17a, 01-211 Warszawa.
Med Wieku Rozwoj. 2012 Jul-Sep;16(3):183-95.
Inherited distubances in skin structure and its function are the main cause of diseases classified as genodermatoses. The following clinical entities are classified as genodermatoses: epidermolysis bullosa, keratotic disorders, disorders of skin color, ectodermal genodermatoses, genodermatoses associated with connective tissue, vascular genodermatoses and genodermatoses with skin manifestation and elevated cancer risk. One of the most clinically heterogenous group of genodermatoses, is epidermolysis bullosa. Four main subtypes were described: simplex, dystrophic, junctional and Kindler syndrome. These diseases are caused by mutations in the genes encoding proteins forming junctions between the dermis and epidermis (eg. COL7A1, COL17A1, KRT14, KRT5 or genes coding for 332 laminin). They are inherited in an autosomal recessive or dominant manner. The disease that is inherited as a dominant, sex dependent trait, is incontinenia pigmenti (Bloch-Sulzberger syndrome) characterized by the presence of extensive pigmentation changes already in the neonatal period. In patients with incontinenia pigmenti, mutations in the NEMO gene are found. The protein encoded by NEMO is involved in the negative regulation of activity of the NFκB transcription factor that is responsible for apoptosis and cell proliferation control. In the regulation of cell proliferation, the neurofibromin (NF1) - the suppressor of RAS/MAPK signaling pathway activity, is also involved. The mutations in the NF1 gene are identified in neurofibromatosis type I - a genodermatosis with higher risk of cancer development and tumor formation. Herein, a review of selected genodermatoses in the context of their molecular pathology is presented.
皮肤结构及其功能的遗传性紊乱是被归类为遗传性皮肤病的疾病的主要原因。以下临床病症被归类为遗传性皮肤病：大疱性表皮松解症、角化性疾病、皮肤颜色紊乱、外胚层遗传性皮肤病、与结缔组织相关的遗传性皮肤病、血管性遗传性皮肤病以及伴有皮肤表现和癌症风险升高的遗传性皮肤病。遗传性皮肤病中临床异质性最强的一组疾病之一是大疱性表皮松解症。已描述了四种主要亚型：单纯型、营养不良型、交界型和Kindler综合征。这些疾病是由编码形成真皮和表皮之间连接的蛋白质的基因突变引起的（例如COL7A1、COL17A1、KRT14、KRT5或编码层粘连蛋白3-3-2的基因）。它们以常染色体隐性或显性方式遗传。以显性、性别依赖性性状遗传的疾病是色素失禁症（布洛赫-舒尔茨贝格综合征），其特征是在新生儿期就已出现广泛的色素沉着变化。在色素失禁症患者中，发现了NEMO基因突变。NEMO编码的蛋白质参与对负责细胞凋亡和细胞增殖控制的NFκB转录因子活性的负调控。在细胞增殖的调控中，神经纤维瘤蛋白（NF1）——RAS/MAPK信号通路活性的抑制剂——也参与其中。在I型神经纤维瘤病（一种癌症发生和肿瘤形成风险较高的遗传性皮肤病）中可鉴定出NF1基因的突变。本文对选定的遗传性皮肤病的分子病理学背景进行了综述。
