Investigation of Genetic Defects in Severe Combined Immunodeficiency Patients from Turkey by Targeted Sequencing

Abstract Primary immunodeficiencies ( PID s) represent a large group of disorders with an increased susceptibility to infections. Severe combined immunodeficiency ( SCID ) is the most severe form of primary immunodeficiencies ( PID s) with marked T‐cell lymphopenia. Investigation of the genetic aetiology using classical Sanger sequencing is associated with considerable diagnostic delay. We here established a custom‐designed, next‐generation sequencing (NGS)‐based panel to efficiently identify disease‐causing genetic defects in PID patients and applied this method in SCID patients of Turkish origin with previously undefined genetic aetiology. We used HaloPlex enrichment technology, a targeted, NGS ‐based method which was designed to diagnose patients with SCID and other PID s. Our HaloPlex panel included a total of 356 PID ‐related genes, and we searched disease‐causing mutations in 19 Turkish SCID patients without a genetic diagnosis. The coverage of targeted regions ranged from 97.47% to 99.62% with an average of 98.31% for all patients. All known SCID genes were covered with a percentage of at least 97.3%. We made a genetic diagnosis in six of 19 (33%) patients, including four novel disease‐causing mutations identified in RAG 1 , JAK 3 and IL 2 RG , respectively. We showed that this NGS ‐based method can provide rapid genetic diagnosis for patients suffering from SCID , potentially facilitating clinical treatment decisions.