A single‐center pilot study in Malaysia on the clinical utility of whole‐exome sequencing for inborn errors of immunity

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole‐exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management. Whole‐exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 Malaysian pediatric patients clinically diagnosed with inborn errors of immunity (IEI). This study demonstrated a diagnostic yield of 46.7% (14/30) and revealed a 50% discordance between the provisional clinical diagnosis and genetic diagnosis. Hence, the capacity to diagnose IEI has been enhanced using WES, allowing more patients to receive appropriate therapy and disease management.