Notably, TYK2 deficiency does not always cause hyper-IgE [15]; PGM3 deficiency, a glycosylation defect, causes a broad phenotype that may include hyper-IgE in its spectrum [16]; and DOCK8 deficiency has been re-categorized from HIES to combined immunodeficiency [17], highlighting the challenge of grouping such heterogeneous disorders by the shared feature of raised IgE. This evidence concerns the gene IGHE and immune system disorder.