...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of investigative dermatology. >Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients.
【24h】

Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients.

机译：Netherton综合征患者中SPINK5基因突变与临床表现之间的相关性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Netherton syndrome (NS) is a congenital ichthyosiform dermatosis caused by serine protease inhibitor Kazal-type 5 (SPINK5) mutations. Tissue kallikreins (KLKs) and lymphoepithelial Kazal-type-related inhibitor (LEKTI) (SPINK5 product) may contribute to the balance of serine proteases/inhibitors in skin and influence skin barrier function and desquamation. SPINK5 mutations, causing NS, lead to truncated LEKTI; each NS patient possesses LEKTI of a different length, depending on the location of mutations. This study aims to elucidate genotype/phenotype correlations in Japanese NS patients and to characterize the functions of each LEKTI domain. Since we were unable to demonstrate truncated proteins in tissue from patients with NS, we used recombinant protein to test the hypothesis that the length of LEKTI correlated with protease inhibitory activity. Genotype/phenotype correlations were observed with cutaneous severity, growth retardation, skin infection, stratum corneum (SC) protease activities, and KLK levels in the SC. Predominant inhibition by LEKTI domains against overall SC protease activities was trypsin-like (Phe-Ser-Arg-) activity by LEKTI domains 6-12, plasmin- and trypsin-like (Pro-Phe-Arg-) activities by domains 12-15, chymotrypsin-like activity by all domains, and furin-like activity by none. KLK levels were significantly elevated in the SC and serum of NS patients. These data link LEKTI domain deficiency and clinical manifestations in NS patients and pinpoints to possibilities for targeted therapeutic interventions.
机译：Netherton综合征（NS）是由丝氨酸蛋白酶抑制剂Kazal 5型（SPINK5）突变引起的先天性鱼鳞状皮肤病。组织激肽释放酶（KLKs）和淋巴上皮Kazal型相关抑制剂（LEKTI）（SPINK5产品）可能有助于皮肤丝氨酸蛋白酶/抑制剂的平衡并影响皮肤屏障功能和脱皮。导致NS的SPINK5突变导致LEKTI缩短;根据突变的位置，每位NS患者拥有不同长度的LEKTI。这项研究旨在阐明日本NS患者的基因型/表型相关性，并表征每个LEKTI域的功能。由于我们无法在NS患者的组织中证实截短的蛋白，因此我们使用重组蛋白来检验LEKTI长度与蛋白酶抑制活性相关的假说。基因型/表型的相关性与皮肤严重程度，生长迟缓，皮肤感染，角质层（SC）蛋白酶活性和SC中的KLK水平有关。 LEKTI结构域对总体SC蛋白酶活性的主要抑制作用是LEKTI结构域6-12的胰蛋白酶样（Phe-Ser-Arg-）活性，结构域12-15的纤溶酶和胰蛋白酶样（Pro-Phe-Arg-）活性。 ，所有域的胰凝乳蛋白酶样活性，无域的弗林蛋白酶样活性。 NS患者的SC和血清中的KLK水平显着升高。这些数据将NS患者的LEKTI域缺乏症和临床表现联系起来，并指出了针对性治疗干预的可能性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号