PDF(Pubmed)
Abstract：
Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood. In our study, we conducted whole-exome sequencing on a cohort of 17 AOID patients with pustular reactions (AOID-PR) and 24 PP patients. We found that 76% and 58% of the AOID-PR and PP patients, respectively, carried rare genetic variations within the filaggrin (FLG) gene family. A total of 12 out of 21 SNPs on FLG had previously received clinical classifications, with only p.Ser2706Ter classified as pathogenic. In contrast, none of the FLG3 SNPs identified in this study had prior clinical classifications. Overall, these variations had not been previously documented in cases of pustular disorders, and two of them were entirely novel discoveries. Immunohistochemical analysis of skin biopsies revealed that FLG variants like p.Ser860Trp, p.Gly3903Ter, p.Gly2440Glu, and p.Glu2133Asp caused reductions in FLG levels similar to the pathogenic FLG p.Ser2706Ter. These results highlight rare FLG variants as potential novel genetic risk factors contributing to pustule formation in both AOID and PP.
摘要：
反应性脓疱爆发（RPE）可以在各种条件下表现出来，包括脓疱型银屑病（PP）和因抗干扰素-γ自身抗体（AOID）引起的成人发作性免疫缺陷综合征。这些RPE可以归因于不同的原因，其中之一是遗传因素。然而,脓疱性皮肤病的遗传基础仍然知之甚少。在我们的研究中,我们对一组17例有脓疱反应的AOID患者(AOID-PR)和24例PP患者进行了全外显子组测序.我们发现76%和58%的AOID-PR和PP患者，分别,在聚丝蛋白（FLG）基因家族中携带罕见的遗传变异。在FLG的21个SNP中，共有12个以前接受过临床分类，只有p.Ser2706Ter被归类为致病性。相比之下,本研究中鉴定的FLG3SNP均无先前的临床分类。总的来说,这些变化以前没有在脓疱病病例中记录过，其中两个是全新的发现。皮肤活检的免疫组织化学分析显示，FLG变体如p.Ser860Trp，p.Gly3903Ter,p.Gly2440Glu,和p.Glu2133Asp引起与致病性FLGp.Ser2706Ter相似的FLG水平降低。这些结果强调了罕见的FLG变异体是导致AOID和PP脓疱形成的潜在新遗传风险因素。
