Recombinase-activating gene 1 immunodeficiency: different immunological phenotypes in three siblings.

[omenn syndrome]

We report different immunological phenotypes in three siblings from consanguineous family with recombinase-activating gene 1 (RAG 1 ) gene mutations . Null mutations of RAG genes result in severe combined immunodeficiency (SCID ) with absent T and B cells . Hypomorphic mutations with retained activity of RAG genes may lead to a 'leaky ' SCID with some features of Omenn syndrome (OS ) or typical OS . In our three patients , homozygous , hypomorphic RAG 1 gene mutation (g .368 -369 delAA ) was detected . Two patients presented with T -B-SCID phenotype while the youngest patient developed T +B +NK +SCID phenotype with expansion of autologous T -cell receptor (TCR ) gammadelta-positive T cells , increased immunoglobulin levels and retained ability for antibody production . Similar to originally reported patients with this newly recognized immune phenotype , our patient developed disseminated cytomegalovirus (CMV ) infection and autoimmune cytopenia .In infants with disseminated cytomegalovirus infection and autoimmune cytopenia , even if basic immunologic investigation appears normal , RAG 1 immunodeficiency should be considered .