• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>American Journal of Human Genetics >Nonsense Mutations in AAGAB Cause Punctate Palmoplantar Keratoderma Type Buschke-Fischer-Brauer
【2h】

Nonsense Mutations in AAGAB Cause Punctate Palmoplantar Keratoderma Type Buschke-Fischer-Brauer

机译：AAGAB中的无意义突变导致点状掌足角化性皮肤型Buschke-Fischer-Brauer

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Punctate palmoplantar keratodermas (PPKPs) are rare autosomal-dominant inherited skin diseases that are characterized by multiple hyperkeratotic plaques distributed on the palms and soles. To date, two different loci in chromosomal regions 15q22-15q24 and 8q24.13-8q24.21 have been reported. Pathogenic mutations, however, have yet to be identified. In order to elucidate the genetic cause of PPKP type Buschke-Fischer-Brauer (PPKP1), we performed exome sequencing in five affected individuals from three families, and we identified in chromosomal region 15q22.33-q23 two heterozygous nonsense mutations—c.370C>T (p.Arg124∗) and c.481C>T (p.Arg161∗)—in AAGAB in all affected individuals. Using immunoblot analysis, we showed that both mutations result in premature termination of translation and truncated protein products. Analyses of mRNA of affected individuals revealed that the disease allele is either not detectable or only detectable at low levels. To assess the consequences of the mutations in skin, we performed immunofluorescence analyses. Notably, the amount of granular staining in the keratinocytes of affected individuals was lower in the cytoplasm but higher around the nucleus than it was in the keratinocytes of control individuals. AAGAB encodes the alpha-and gamma-adaptin-binding protein p34 and might play a role in membrane traffic as a chaperone. The identification of mutations, along with the results from additional studies, defines the genetic basis of PPKP1 and provides evidence that AAGAB plays an important role in skin integrity.
机译：点状掌plant角化病（PPKPs）是罕见的常染色体显性遗传性皮肤病，其特征是分布在手掌和脚掌上的多个过度角化斑块。迄今为止，已经报道了染色体区域15q22-15q24和8q24.13-8q24.21中的两个不同基因座。然而，致病性突变尚未确定。为了阐明PPKP型Buschke-Fischer-Brauer（PPKP1）的遗传原因，我们在来自三个家族的五个受影响个体中进行了外显子组测序，并在染色体区域15q22.33-q23中鉴定出两个杂合的无义突变-c.370C AAGAB中所有受影响个体的> T（p.Arg124 ∗ ）和c.481C> T（p.Arg161 ∗ ）—。使用免疫印迹分析，我们表明这两种突变均会导致翻译和蛋白产物截断的过早终止。受影响个体的mRNA分析表明，该疾病等位基因不是可检测到的，还是只能以低水平检测到的。为了评估皮肤突变的后果，我们进行了免疫荧光分析。值得注意的是，与对照个体的角质形成细胞相比，受影响个体的角质形成细胞中的颗粒染色量在细胞质中较低，但在细胞核周围较高。 AAGAB编码α-和gamma-adaptin结合蛋白p34，并可能在膜运输中作为伴侣发挥作用。突变的鉴定以及其他研究的结果定义了PPKP1的遗传基础，并提供了AAGAB在皮肤完整性中起重要作用的证据。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

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