Current Genetic Defects in Common Variable Immune Deficiency Patients on the Geography Between Europe and Asia

Abstract Identification of the causes of monogenetic common variable immune deficiency (CVID) patients has rapidly increased in the last years by means of worldwide availability of appropriate genetic diagnostic methods. However, up to date, very limited numbers of reports demostrating the role of geography, ethnicity and consanguinity have been published. Here, we reported the first study of Turkish CVID patients and compared them with the results of three countries from America, Europe and Asia. A total of 100 children diagnosed as CVID according to the criteria of European Society for Immunodeficiencies were enrolled and they were genetically analyzed by using Targeted Next Generation Sequencing and Whole Exome Sequencing. The median age of our patients was 5.8 years (range, 3.0-16.0 years) at clinical diagnosis and 9.0 years (range, 4.8-21.0 years) at the time of genetic diagnosis. The consanguianity rate was 24%. Disease-causing pathogenic mutations were defined in 40% of patients in a total of 17 different genes. Sixteen of 40 identified mutations were novel (40%). We determined 18 surface molecular defects, 10 cytosolic defects, 9 nuclear defects and 3 others. In our cohort, the most common gene was TACI (15/40 in mutation identified cases and 15/100 in all cases) followed by the others such as PLCү2, LRBA, TCF3 and STAT1. In contrast to our expectations, our results were more similar to American and European population rather than Asians, although we also have high consanguinity rates and live on the geography between Europe and Asia. Genetic investigation is a great challenge, because of the complexity and heterogenity of the disease and each country has to know their own current genetic landscape in CVID for a better and successful management of the patients.