Focusing on HIES, the prototypic syndrome is caused by dominant-negative germline mutations in Signal transducer and activator of transcription 3 (STAT3), resulting in an autosomal dominant Hyper-IgE (AD-HIES or STAT3-HIES) syndrome, formerly known as Job syndrome, characterized by eczema, skin abscesses [Fig. 2], recurrent pneumonia leading to pneumatocoeles, and skeletal and connective tissue abnormalities, such as bone fragility, scoliosis, and decidual teeth retention.14 The gene discussed is STAT3; the disease is Alzheimer disease.