Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKII proteins in the skin lesions of HHD patients. Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels. In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKII levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

中文翻译：

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Hailey-Hailey病患者中ATP2C1突变的鉴定。

家族性良性慢性天疱疮，也称为Hailey-Hailey病（HHD），是临床上罕见的大疱性皮肤病。但是，该机制尚未阐明。该研究旨在检测HHD患者ATP2C1基因外显子的新突变。通过检查hSPCA1，miR-203，p63，Notch1和HKII蛋白在HHD患者皮肤病变中的表达谱，探索HHD发病机理的可能机制。从HHD患者的外周血中提取基因组DNA。通过PCR扩增HHD患者的所有ATP2C1基因外显子，并对产物进行纯化和测序。通过使用HHD患者的皮肤病变组织对所有感兴趣的相关信号蛋白进行染色，并测定miR-203的水平。一个同义突变c.G2598A（在外显子26中），一个无意义突变c.C635A和两个错义突变c.C1286A（p。A429D）和c。确定了A1931G（p。D644G）。无义突变改变了密码子UCG以终止密码子UAG，导致功能区A的多肽链过早。这两个错义突变位于hSPCA1的P区（磷酸化区）和Mn结合位点。与正常的人类对照相比，HHD患者的hSPCA1水平显着降低，同时miR-203水平升高，p63和HKII水平降低。在我们的研究中，我们发现了HHD中的四个突变。同时，我们发现miR-203水平升高，而p63和HKII水平降低。此外，p63负调控的Notch1被下调。这些因素可能参与HHD发病机理的信号传导途径。