Genotype spectrums in 151 patients with pustular psoriasis from China

Summary: Abstract Body: Objective: There is a paucity of knowledge on the genetic heterogeneity of pustular psoriasis (PP), this study aims to describe the genetic spectrums. Methods: The analysis of currently known variations in PP-related genes via whole genome sequencing (WGS) was conducted based on a bidirectional cohort research of 151 PP patients. Results: A total of 114 generalized PP (GPP) were identified among 151 PP patients, including 67 GPP-only and 47 GPP+PsV (psoriasis vulgaris). Additionally, 16 patients were diagnosed with ACH (acrodermatitis continua of Hallopeau), and 21 were PPP (palmoplantar pustulosis). IL36RN-positive patients account for 83, including GPP-only (47), GPP+PsV (19), ACH (12) and PPP (5). While the IL36RN-negative patients account for 68, consisting of 20 GPP-only, 28 GPP+PsV, 4 ACH and 16 PPP, among them, 16 were positive for CARD14, and fewer were positive for other pathogenic genes of MPO, AP1S3, SERPINA3 and others. In total, 24.5% (37/151) patients were CARD14-positive, 21.6% (8/37) were homozygous (all of which were c.2458C>T variants), a half of the homozygous were diagnosed with PPP. We further analyzed the genetic variations in PPP patients. 23.8% (5/21) were IL36RN-positive (2 homozygous), while 28.6% (6/21) were CARD14-positive (4 homozygous). Given that tongue abnormalities have been recognized in PP, we analyzed the genetic profiles of 113 patients who underwent tongue examination. 40.7% (48/118) patients exhibited geographic/fissured tongue, including 28 cases of GPP-only, 10 of GPP+PsV, 7 of ACH, and 3 of PPP. The incidence of geographic/fissured tongue was significantly higher in IL36RN-positive patients compared to IL36RN-negative (67.2% vs 10.2%). Conclusions: This study presents the genotype spectrums of PP in the Chinese population, reveals complex genotype-phenotype correlations and provides new insights into the genetic background of PPP. Yusha Chen³, Jia Geng¹, Yue Zhang², Fengxiao Bu¹, Wei Li³ 1. Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China. 2. Department of Dermatology, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China. 3. Department of Dermatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China. Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics