Novel mutatıons and diverse clinical phenotypes in recombinase-activating gene 1 deficiency.

[omenn syndrome]

Severe combined immunodeficiency is within a heterogeneous group of inherited defects throughout the development of T - and /or B-lymphocytes . Mutations in recombinase-activating genes 1 or 2 (RAG 1 /2 ) represent approximately 10 % of all SCID cases . RAG 1 /2 are essential for V (D )J rearrangement of the B- and T -cell receptors .T he aim of this study was to review clinical , immunological and molecular findings of Turkish SCID patients with RAG 1 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 RAG 1 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 .