Ayat Kadhi ^1,2,3 Edward Eid ^4,5 Michel J. Massaad ⁶ Inaam El-Rassy ⁷ Dana Maria Khoury ⁵ Yutaka Shimomura ⁸ Nelly Rubeiz ⁵ Mazen Kurban ^4,5,9 Georges Michel Nemer ^10,4*

• ¹ Hamad bin Khalifa University, Doha, Qatar
• ² Sidra Medicine, Doha, Qatar
• ³ University of Doha for Science and Technology, Doha, Qatar
• ⁴ Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
• ⁵ Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon
• ⁶ Department of Experimental Pathology and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
• ⁷ Pillar Genomic Institute (PGI), Faculty of Medicine, American University of Beirut, Beirut, Lebanon, Beirut, Lebanon, Lebanon
• ⁸ Department of Dermatology, Yamaguchi University Graduate School of Medicine, Ube, Japan, Ube, Japan, Japan
• ⁹ Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar, 1Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar, Doha, Qatar
• ¹⁰ 1Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar, Doha, Qatar

Psoriasis and chronic mucocutaneous candidiasis (CMC), although distinct in their clinical manifestations, often coexist within specific patient cohorts. Despite this intriguing clinical observation, their genetic etiologies have been studied separately, neglecting the shared inflammatory mediator, interleukin 17A-F (IL17A-F). Consequently, the immunogenetic foundations underlying these conditions have remained enigmatic.In this study, we present the concomitant presence of psoriasis and CMC phenotypes in a 5-yearold female born to consanguineous parents. Utilizing whole exome and transcriptomic sequencing, we meticulously unravel the genetic underpinnings of these complex pathologies and the underlying molecular pathways.Remarkably, we unveil a novel bi-allelic variant (NM_014339.6, c.1173C>G A) within the interleukin 17 receptor type A (IL17RA) gene that leads to a premature stop codon (p. Tyr391Ter). Our investigations demonstrate that this variant yields a fully functional protein, evident by the presence of IL17RA in the patient's peripheral blood mononuclear cells (PBMC) and the mutant ability of IL17RA to dimerize with both wild-type protein and its partners IL17RC and RD. Employing RNA sequencing on a skin biopsy, we confirm a distinct psoriasisassociated transcriptomic signature, intertwined with other nodes of inflammatory response, including reactions to fungal infections. This report unveils an unprecedented genetic link serving as a common denominator for both psoriasis and CMC. The paramount role played by IL17RA emerges as a milestone towards a nuanced understanding of these conditions. This discovery not only fills a critical knowledge gap but also lays the foundation for future personalized therapeutic interventions, ushering in a new era of precision medicine for patients with these intertwined diseases.