反常性痤疮，以反复发生皮肤脓肿,窦道及瘢痕形成为特征表现。其发病机制认为是由于毛囊漏斗部的上皮细胞过度角化增生造成皮脂排出不畅，继发细菌感染引起。我国学者发现其发病是由编码γ一分泌酶不同亚单位的基因（NCSTN，PSEN1，PSENEN）发生功能突变引起的。我们在临床遇到2个反常性痤疮大家系，通过基因筛查发现了PSENEN基因的2个新发突变位点（c.194T>G，c.167-2A>G）且PSENEN对天然免疫的影响尚未见报道。本课题第一部分拟从分子与蛋白水平阐述这两个新发突变对PSENEN表达的差异以及对notch信号通路的影响，明确新发突变位点发病机制；第二部分通过LPS分别刺激过表达与低表达PSENEN的巨噬细胞Raw264.7，观察其分泌抗炎因子与促炎因子的差异，探讨PSENEN在天然免疫中发挥的作用。本研究扩大了反常性痤疮的遗传数据库，而且对反常性痤疮的免疫机制研究具有一定的意义。

Acne inversa is be characterized by recurring skin abscess, fistula and scar.The etiology and pathogenesis of the disease is thought to be blocking of hair follicles and sebaceous glands with secondary bacterial infection. Chinese scholar found that some familial acne inversa was caused by the mutation of genes encoding gamma secretase subunit (NCSTN,PSEN1,PSENEN). We found two new mutations (c.194T>G,c.167-2A>G) of the PSENEN gene in two big Chinese families with acne inversa. Besides, the relationship of the PSENEN gene with natural immune has not yet been reported.To study the role of these new mutations,we observed the difference expression of the PSENEN and a serie of changes of Notch signaling pathway on the molecular and protein level.Then,the over expression and knocking down of PSENEN in Raw264.7 cells would find out the different secretion between anti-inflammatory cytokine and pro-inflammatory cytokine after the stimulating with LPS. This study would not only extend the genetic database of acne inversa but also identify the immunologic mechanism of the PSENEN gene in this diease on the molecular and protein level.

反常性痤疮，以反复发生皮肤脓肿,窦道及瘢痕形成为特征表现。其发病机制认为是由于毛囊漏斗部的上皮细胞过度角化增生造成皮脂排出不畅,继发细菌感染引起。我国学者发现其发病是由编码γ一分泌酶不同亚单位的基因(NCSTN,PSEN1,PSENEN)发生功能突变引起的。我们在临床遇到2个反常性痤疮大家系，通过基因筛查发现了PSENEN基因的2个新发突变位点(c.194T>G,c.167-2A>G)，从分子与蛋白水平阐述新发突变对PSENEN表达的差异以及对notch信号通路的影响。通过构建野生型与突变型融合质粒，转染293细胞，发现PSENEN突变型表达较野生型低，在RNA水平上， Notch2，Hes1，Hey1，Hey2这些基因在突变型细胞内表达升高，Notch3在突变型细胞内表达下降，在蛋白水平整体趋势上，cleaved notch1，notch1，notch2，notch3在突变型细胞表达降低。本研究扩大了反常性痤疮的遗传数据库，而且对反常性痤疮的免疫机制研究具有一定的意义。