Novel mutat？ons and diverse clinical phenotypes in recomb？nase-activating gene 1 deficiency

The aim of this study was to review clinical, immunological and molecular findings of Turkish SCID patients with RAG1 defects and to draw attention to novel mutations, genotype-phenotype correlations and the high rate of BCG infections within this group.Eleven patients (F/M: 6/5) were included. Molecular, immunological and clinical data were evaluated.Five patients were classified as T-B-NK + SCID, four patients as T + B-NK + SCID (two of these patients were diagnosed as classical Omenn syndrome) and two patients as T + B + NK + SCID with respect to clinical presentations and immunological data. Mean age of the whole study group, mean age at onset of symptoms and mean age at diagnosis were: 33.0 ± 42.8, 3.1 ± 3.3 and 10.4 ± 13.5 months, respectively. Consanguinity rate was 54%. Some novel mutations were found in RAG1 gene in addition to previously reported mutations. Genotype-phenotype correlation was not significantly apparent in most of the cases. BCG infection was observed in 36.4% of patients (two BCG-osis and two BCG-itis).Epigenetic factors such as compound genetic defects, enviromental factors, and exposure to recurrent infections may modify phenotypical characteristics of RAG deficiencies. Inoculation of live vaccines such as BCG should be postponed until primary immunodeficiency disease is excluded with appropriate screening tests in suspected cases.Severe combined immunodeficiency (SCID) syndromes embrace common phenotypic presentation of a range of genetic disorders [1]. According to recent immunological and genetic findings, SCID can be subdivided into 11 conditions. These conditions are abnormally increased apoptosis of the lymphocytes (reticular dysgenesis caused by adenylate kinase 2 (AK2), adenosine-deaminase-deficiency), defects of cytokine signaling (X-linked SCID, IL7-receptor-α, JAK3- deficiency), defects in T-cell-receptor (TCR) assembly and signaling (RAG1/2, DNAPKcs, Artemis and Cernunnos, CD3 defects) and general T-cell signaling defects asso