Whole-exome sequencing assists in the diagnosis of hyperimmunoglobulin E syndrome: Insights into dual genetic abnormalities

Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder characterized by recurrent infections, severe eczema, and elevated serum immunoglobulin E (IgE) levels. Genetic testing traditionally focuses on known genes such as <i>STAT3</i> and <i>DOCK8</i>, responsible for the majority of autosomal-dominant (AD-HIES) and autosomal-recessive (AR-HIES) cases, respectively. However, a significant subset of patients with HIES-like symptoms remain genetically unexplained. Whole-exome sequencing (WES) has emerged as a transformative diagnostic tool, enabling the identification of both novel and incidental genetic mutations. This report highlights the role of WES in diagnosis of AD-HIES, showcasing its utility in detecting a <i>STAT3</i> mutation while revealing a concurrent <i>BRCA2</i> pathogenic variant. While the <i>STAT3</i> mutation confirmed the diagnosis of AD-HIES, the incidental <i>BRCA2</i> finding underscores the importance of genetic counseling and long-term surveillance.