Inborn errors of immunity in south africa: genetics and the expanding universe

Inborn errors of immunity (IEI) represent a diverse group of disorders resulting from monogenic defects in immune system genes. These defects cause individuals to be more susceptible to severe, persistent, unusual and recurrent infections, malignancies and autoimmune/autoinflammatory conditions. Recent advances in next -generation sequencing (NGS) technologies have transformed IEI diagnoses, as can be seen in the large increase of new variants identified in these disorders. However, many suspected IEI patients still lack a molecular diagnosis, emphasising the need for unbiased investigative approaches. The early diagnosis of IEI enables more effective treatments and ensures more precise genetic counselling, which help families to understand the disease, family planning and informed decision-making about testing. The establishment of registries is critical to capturing data on IEI patients, which can inform clinical care, raise awareness and respond to research questions in the field. In developing countries such as South Africa, the adoption of NGS technologies has the potential to transform the diagnosis and management of IEI, ultimately improving patient outcomes. This review highlights the significance of NGS technologies in the diagnosis and management of IEI, the importance of genetic counselling and the role of registries in advancing our understanding of these rare disorders, particularly in underserved regions.