Comprehensive clinical phenotype, genotype and therapy in Yao syndrome

Objective: Yao syndrome (YAOS) is formerly called nucleotide-binding oligomerization domain containing 2 (NOD2)-associated autoinflammatory disease.We report a large cohort of YAOS. Methods: We conducted a retrospective analysis of a cohort of adult patients with systemic autoinflammatory diseases (SAIDs). All patients underwent testing for a periodic fever syndrome gene panel. Results: A total of 194 patients carried NOD2 variants, 152 patients were diagnosed with YAOS, and 42 had mixed autoinflammatory diseases with combined variants in NOD2 and other SAID-associated genes. Demographic, clinical and molecular data were summaried. In sub-group analysis of the 194 patients, individual patients were often identified to carry two or more variants that usually included IVS8 + 158/R702W, IVS8 + 158/L1007fs, IVS8 + 158/V955I, IVS8 + 158/other, or NOD2/variants in other SAID genes. Ninety-nine patients carried single variants. Taken together, these variants contribute to the disease in combination or individually. Conclusion: This largest cohort has provided comprehensive clinical and genotyping data in YAOS. Variants in the NOD2 gene can give rise to a spectrum from inflammatory bowel disease to autoinflammatory disease.This report further raises awareness of the underdiagnosed disease in the medical community.