Retrospective evaluation of the genetic analysis results of the patients with inborn errors of immunity

Aim: Evaluating the results of the genetic tests performed on patients with inborn errors of immunity (IEI), we aimed to determine the tangible contribution of genetic methods evolving with the devoloping technology, to diagnosis of IEI patients and to evaluate the effectiveness of new generation sequencing methods, especially Whole Exome Sequencing (WES), in the diagnosis of the cases where a target disease / gene could not be detected. Method: The genetic test results of a total of 255 patients who were admitted with a pre-diagnosis of IEI until the beginning of 2015 and the end of 2020 were examined retrospectively by comparing them with the literature data. Results: Of the 255 patients whose genetic analyzes were made, 154 were male (60%) and 101 were female (40%). As a result of the FISH analysis performed in 9 patients with clinical suspicion of DiGeorge Syndrome (DGS), deletion in the 22q11 region was detected in 3 patients and DGS was diagnosed. By performing single gene analyzes in 206 patients whose target genes were determined with their clinical features, results that were thought to explain the clinic in 29 patients were obtained. While no SNV was detected in 9 patients who underwent single gene analysis, FANCA gene MLPA analysis was performed simultaneously and deletion was detected in 4 patients and a diagnosis of Fanconi anemia was made. A total of 71 patients, including 31 patients who met the conditions from patients who could not be diagnosed via single gene analysis, and 40 patients who had direct WES analysis, were able to diagnose 22 patients as a result of WES analysis. Conclusion: Considering the clinical and genetic heterogeneity, it is necessary to establish a molecular diagnosis for the correct follow-up and treatment of patients with IEI. Whole exome sequencing, in particular, is an effective tool in the diagnosis of patients with IEI, as enabling the evaluation of variants in all known and new genes, the cumulative interpretation of variants with the panogromic perspective obtained and the re-analysis with updated information. Integrating the bioinformatics tools with WES analysis could also provide a prediction of structural variations in disease-related genes. Key Words: immunodeficiency, next generation sequencing, WES