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首页> 外文期刊>Molecular biology reports >Papillon-Lefevre syndrome (PLS) with novel compound heterozygous mutation in the exclusion and Peptidase C1A domains of Cathepsin C gene
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Papillon-Lefevre syndrome (PLS) with novel compound heterozygous mutation in the exclusion and Peptidase C1A domains of Cathepsin C gene

机译：Papillon-Lefevre综合征（PLS）具有新型化合物杂合酶突变，在组织蛋白酶C基因的排除和肽酶C1A结构域中

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摘要

Papillon Lefevre syndrome (PLS) manifests with palmoplantar keratoderma, combined with a rapidly progressive periodontitis associated with mutations in Cathepsin C (CTSC) gene. This article reports a 15-year old male proband with typical PLS traits having a novel compound heterozygote with p.Q49X mutation in exon 1 and p.Y259C missense mutation in exon 6 ofCTSCgene respectively. The exon 1 mutation, p.Q49X, (found in proband's mother) was located in exclusion domain and exon 6 mutation, p.Y259C (found in proband's father), was present in peptidase C1A, papain C-terminal domain. Interestingly, missense mutation p.Y259C identified in this study was found to be not reported so far. Upon computational analysis, this missense mutation was found to be lethal. Moreover, our protein modelling approach using mutant protein revealed the presence of monomeric structure on contrary to the tetrameric structure of the wild type protein. In addition, in vitro functional characterization of mutant p.Y259C expressed in HEK293 cells showed a significant reduction in CTSC activity (0.015 +/- 0.009 mU/ml) when compared with wild type protein (0.21 +/- 0.008 mU/ml). Thus, in this study, we have demonstrated that the pathogenic missense mutant p.Y259C might cause PLS by impaired CTSC function.
机译：Papillon Lefevre综合征（PLS）用棕榈阶Keratoderma表现出与迅速逐步的牙周炎，与组织蛋白酶C（CTSC）基因的突变相关。本文报告了一个15岁的男性概念，具有分别在外显子1和P.Y259C中具有P.Q49x突变的新化合物杂合子的典型PLS特征。外显子1突变，P.Q49x（在母亲的母亲中发现）位于排除领域和外显子6突变中，P.Y259C（在父亲的父亲中发现），存在于肽酶C1A，木瓜蛋白酶C-末端结构域中。有趣的是，目前发现本研究中确定的Missense突变P.Y259C未报告。在计算分析后，发现这种畸形突变是致命的。此外，我们使用突变蛋白的蛋白质建模方法显示了与野生型蛋白质的四聚结构相反的单体结构存在。此外，与野生型蛋白质（0.21 +/-0.008μm/ mL）相比，HEK293细胞中表达的突变体P.Y259C的体外功能表征在HEK293细胞中表达的显着降低（0.015 +/-0.009μm/ ml）。因此，在本研究中，我们已经证明了致病性畸变突变体P.Y259C可能会导致CTSC功能受损。

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