Rugg Elizabeth L, Horn Helen M, Smith Frances J, Wilson Neil J, Hill Alison J M, Magee Gareth J, Shemanko Carrie S, Baty David U, Tidman Michael J, Lane E Birgitte
Cancer Research UK Cell Structure Research Group, School of Life Sciences, University of Dundee, Dundee, UK.
J Invest Dermatol. 2007 Mar;127(3):574-80. doi: 10.1038/sj.jid.5700571. Epub 2006 Oct 12.
Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS Köbner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70% of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.
单纯性大疱性表皮松解症（EBS）是一种遗传性皮肤病，由角蛋白K5（角蛋白5）和K14（角蛋白14）的突变引起，基底角质形成细胞的脆弱性导致表皮细胞溶解和水疱形成。患者的严重程度差异很大，根据水疱的分布和形态可分为三种主要亚型：EBS Weber-Cockayne型（EBS-WC）、EBS Köbner型（EBS-K）和EBS Dowling-Meara型（EBS-DM）。在苏格兰登记为受显性EBS影响的43个家族中，我们在20个家族中鉴定出了K5/K14突变；结合之前的研究，这涵盖了所有苏格兰EBS患者的70%，使这成为分析最全面的EBS人群。九个突变是新发现的。所有突变都位于先前确定的五个杆状结构域热点内，最严重的水疱形成与螺旋边界基序中的突变有关。在某些情况下，相同的突变在家族内部和家族之间都导致了EBS-WC和/或EBS-K的症状，这表明其他因素对表型有影响。在一些患者中，未在K5、K14或K15中发现突变，这表明其他基因也参与其中。结果证实，EBS最好被视为一种单一疾病，具有一系列表型变异，从一端的严重EBS-DM到另一端的轻度EBS-WC。
