Genetic and immunological characterization of a hyper-IgE Syndrome pedigree

摘要: Understanding the immune system and how it is influenced by genome are key steps for unraveling genetic basis of immunological regulation dysregulation. Advances in tools sequencing strategies potentially allow us to identify novel disease-causing mutations poorly understood diseases such as hyper-IgE syndrome (HIES). HIES a primary deficiency characterized eczema, recurrent skin lung infection, greatly increased serum levels IgE. has been linked Mendelian inheritance STAT3, DOCK8 TYK2, however, most cases do not have known cause. In this study we worked on family which manifested two children consanguineous parents. The patients were diagnosed with HIES, yet no mutation orTYK2 found. Resorting whole-exome found rare coding SNP CARD11, was considered best candidate explain patient’s phenotype due similarities Card11-deficient mouse (atopic dermatitis, IgE Th2-driven response). Based hypothesized that causing patients, however our results rule out CARD11 causable gene clinical phenotype. phenotyping one patient revealed decrease Th2 cells, Tregs naive CD4 + T an increase memory CD8 cells. Together, these suggest category immunologic basis. Additional research disease causation may contribute better understanding production IgE-mediated diseases.