P59 Clinic and genetic characteristics of patients with generalized pustular psoriasis: a bidirectional cohort study

Abstract Generalized pustular psoriasis (GPP) is an infrequent disease with significant genetic predisposition, the IL36RN gene has been evidenced of pathogenicity, additionally, furthermore, eight genes including CARD14, AP1S3, MPO, SERPINA1, SERPINA3, BTN3A3, TNIP1 and TGFBR2 have been successively identified of involved in the pathogenesis of GPP.1,2 However, a considerable proportion of quintessential GPP patients either exhibit no mutations in the aforementioned genes, or been detected of only single-allele heterozygous variation, or have found two or more pathogenic genes. The prevailing view thought GPP follows an oligogenic inheritance pattern rather than a monogenic one. Currently, genetic testing for GPP employs methodologies such as whole-exome sequencing, next-generation sequencing (NGS) targeted gene panel exome sequencing and Sanger sequencing for specific genes like IL36RN. However, the aforementioned methods do not address the identification of unknown genes, variations in non-coding regions, structural variants (SVs), or copy number variations (CNVs). Whole-genome sequencing (WGS), by comparing individual genomic sequences to a reference genome, provides detailed information on single nucleotide variations (SNVs), insertions and deletions (InDels), SVs and CNVs within the genome. The application of WGS to the research of GPP will undoubtedly contribute to the investigation of its unknown mechanisms. In our study, WGS was carried out on a total of 79 patients diagnosed with pustular psoriasis (PP) up to the present, comprising single GPP (35), psoriasis vulgaris (PsV)-GPP (15), and palmoplantar pustulosis (PPP) or acrodermatitis continua (ACH)-GPP (4), single PPP (10) or ACH (2), clinic characteristics including groove or map-like tongue, nail involvements were also recorded for phenotypic matching. Four variant types (c.115+6T>C, c.334G>A, c.227C>T and c.169G>A) of IL36RN in 43 patients (43/79) were identified, among which c.115 + 6T>C exhibited the highest frequency. Among them, 19 patients had c.115 + 6T>C homozygous mutations, 15 patients had c.115 + 6T>C single heterozygous mutation and 2 patients had c.115 + 6T>C and c.227C>T complex heterozygous mutations. A total of 21/43 patients had IL36RN biallelic mutations, and 22/43 patients had IL36RN monoallelic mutations. In addition, some predicted pathogenic mutations were detected in TNIP1, SERPINA1, MPO, TGFBR2, AP1S3 and CARD14 genes.