内瑟顿综合征:报道2例患有葡萄球菌烫伤样皮肤综合征的台湾双胞胎及其SPINK5位点的点突变

作     者：Richard G. Lee J.Y.-Y. 潘敏 

作者机构：Department of Dermatology School of Medicine National Cheng Kung University 138 Sheng-Li Road TainanChina Taiwan 

出 版 物：《世界核心医学期刊文摘（皮肤病学分册）》 (Digest of the World Core Medical JOurnals:Dermatology)

年 卷 期：2005年第1卷第6期

页      面：51-52页

学科分类：1002[医学-临床医学] 100206[医学-皮肤病与性病学] 10[医学] 

主　　题：SPINK5 鱼鳞病样红皮病 迂回线状鱼鳞病 点突变 过敏性体质 角质层分离 葡萄球菌感染 常染色体隐性 直接测序 套叠 

摘      要：Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis and frequent bacterial infections. Pathogenic mutations in SPINKS have recently been identified in NS. SPINKS encodes lymphoepithelial Kazal-type-related inhibitor (LEKTI), a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report two Taiwan Residents brothers with NS. The patients had typical manifestations of NS with an atopic diathesis and recurrent staphylococcal infections, including staphylococcal scalded skin syndrome (SSSS) since birth. Horny layers were obtained by skin surface biopsy for electron microscopy from lesional skin of both patients and from normal controls. All 33 exons and flanking intron boundaries of SPINKS were amplified for direct sequencing. The ultrastructure of the stratum corneum (SC) was characterized by premature degradation of corneo desmosomes (CDs) with separation of corneocytes. A homozygous 2260A→ T (K754X) mutation of SPINK5 was found in both patients. Staphylococcal exfoliative toxin A (ETA) is a serine protease capable of cleaving desmoglein 1, an important adhesive molecule of CDs, and can cause separation of the SC, resulting in SSSS. The premature degradation of CDs found in our patients may be attributable to insufficient LEKTI, and possibly also to colonization/infection of ETA-producing Stophylococcus aureus. Mechanisms involved in the pathogenesis of the skin barrier defect in NS are proposed. Further study is needed to prove this hypothesis.