Abstract：
Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. An early onset of the diseases is correlated with mutations among IL36RN, CARD14, AP1S3, MPO and SERPINA3 genes. Systemic biological agents including anti-TNF-α, anti-IL-17, anti-IL-12/IL-23, anti-IL1R, anti-IL1β and anti-IL-36R act as novel treatment methods for GPP. Herein we report a female infant clinically diagnosed with GPP since she was 10-month-old. Results of whole-exome sequencing (WES) and Sanger sequencing revealed a reported heterozygous IL36RN (c.115+6T>C) and another reported heterozygous SERPINA3 frame-shifting variant (c.1247_1248del). Initial cyclosporin treatment for the patient led to a partial remission of the symptoms. However, the patient reached nearly total remission of pustules and erythema after anti-TNF-α inhibitor etanercept treatment. Results of further RNA sequencing (RNA-seq) done on peripheral blood mononuclear cells correlated with the clinical responses, showing that cyclosporin suppressed a portion of the neutrophil-related genes, while most genes associated with neutrophil activation, neutrophil-mediated immunity and degranulation were downregulated by the subsequent etanercept treatment. We report this case to demonstrate WES and RNA-seq in combination could come in handy in reaching a precise diagnosis and in evaluating or even predicting the molecular alterations underlying clinical treatment effectiveness.
摘要：
广义脓疱型牛皮癣（3GPP）是一种罕见但严重的牛皮癣。这些疾病的早期发作与IL36RN中的突变有关。CARD14、AP1S3、MPO和SERPINA3基因。全身生物制剂，包括抗TNF-α，抗IL-17，抗IL-12/IL-23，抗IL1R，抗-IL1β和抗-IL-36R可作为一种新的3GPP治疗方法。在此，我们报告了一名10个月大的女性婴儿，临床上被诊断出患有PPI。全外显子组测序（WES）和Sanger测序的结果显示了一个报道的杂合IL36RN（c.115+6T>C）和另一个报道的杂合SERPINA3移码变体（c.1247_1248del）。对患者的初始环孢菌素治疗导致症状的部分缓解。然而,抗TNF-α抑制剂依那西普治疗后,患者脓疱和红斑几乎完全缓解.对外周血单核细胞进行进一步的RNA测序（RNA-seq）的结果与临床反应相关，表明环孢菌素抑制了一部分嗜中性粒细胞相关基因，虽然大多数基因与中性粒细胞活化有关，随后的依那西普治疗下调了中性粒细胞介导的免疫和脱颗粒.我们报告这种情况是为了证明WES和RNA-seq的组合可以在达到精确诊断以及评估甚至预测临床治疗有效性的分子改变方面派上用场。
