AUTHOR=Nomani Hafsa , Wu Song , Saif Ashmia , Hwang Frank , Metzger Jane , Navetta-Modrov Brianne , Gorevic Peter D. , Aksentijevich Ivona , Yao Qingping 

TITLE=Comprehensive clinical phenotype, genotype and therapy in Yao syndrome

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1458118

DOI=10.3389/fimmu.2024.1458118

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>Yao syndrome (YAOS) is formerly called nucleotide-binding oligomerization domain containing 2 (<italic>NOD2)</italic>-associated autoinflammatory disease.We report a large cohort of YAOS.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>A total of 194 patients carried <italic>NOD2</italic> variants, 152 patients were diagnosed with YAOS, and 42 had mixed autoinflammatory diseases with combined variants in <italic>NOD2</italic> 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 <italic>NOD2/</italic>variants in other SAID genes. Ninety-nine patients carried single variants. Taken together, these variants contribute to the disease in combination or individually.</p></sec><sec><title>Conclusion</title><p>This largest cohort has provided comprehensive clinical and genotyping data in YAOS. Variants in the <italic>NOD2</italic> 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.</p></sec>