Tu146 - A Polymorphism in Heterozygous IFIH1-Δ14 Leads to Severe Systemic Inflammatory Responses Like Hemophagocytic Lymphohistiocytosis

Seung Hwan Oh – Laboratory medicine – Pusan National University Yangsan Hospital; Kyung-Hwa Shin – Laboratory medicine – Pusan national university hospital; Su-Yeon Jo – Molecular Diagnostics – Seegene Medical Foundation Busan-Gyeongnam Center; Yun Ji Hong – Laboratory medicine – Seoul National University; Shinae Yu – Laboratory medicine – Haeundae PaikHospital

Abstract Text: Even common viral infections that are usually mild and self-limiting can lead to hospitalization and severe clinical outcome in specific situations such as immunosuppression, preterm birth, and chronic diseases. Systematic inflammatory reactions fulfilling criteria for hemophagocytic lymphohistiocytosis (HLH) can be the initial manifestation of primary immunodeficiency. A twelve-month female infant who was previously healthy, demonstrated fever for two weeks and subsequently generalized skin rashes, suggesting a viral infection. However, her manifestation did not resolve but aggravated with sustained fever, pancytopenia, splenomegaly, increased soluble IL-2R, and decreased fibrinogen fulfilling HLH criteria. We identified a heterozygous splicing variant (NM_022168.3:c.2807+1G>A) (rs35732034) in IFIH1 gene associated with innate immunity using targeted panel sequencing and subsequent Sanger confirmation. We also revealed the alternative splicing resulting in skipping of exon 14 (Δ14) with RNA transcript sequencing. This splicing variant inducing loss-of-function mutation has an allele frequency of 0.0044~0.0065 in Korean population. Therefore, we suggest that IFIH1-Δ14 polymorphism should be considered in the case of exceptionally severe clinical courses, especially revealing systemic inflammatory reactions in common viral infections.