Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome.

[omenn syndrome]

A 2 .5 -month old boy presented with recurrent wheezing , protracted diarrhea , erythrodermia , and failure to thrive .Laboratory analysis showed lymphocytopenia with severely reduced T -cell numbers but normal numbers of B and NK cells . Serum IgE was increased and the patient had eosinophilia . These presentations are consistent with atypical severe combined immunodeficiency (SCID )/Omenn Syndrome and the diagnosis was confirmed by demonstration of homozygosity for the R 841 W mutation in the catalytic core of RAG 1 . Comparison of the patient 's immunoglobulin heavy chain rearrangements to those of age-matched controls , cord blood , and adults revealed an almost total lack of nonproductive rearrangements (2 .7 % versus 14 .7 %, 27 .6 %, and 19 .8 % in the controls , respectively ) indicating failure to correct out-of-frame rearrangements by a second rearrangement on the homologous chromosome 14 .We hypothesize that the R 841 W mutation causes a malfunction of RAG 1 that has differential outcome on V (D )J recombination in B and T cells , as the patient had normal B cell numbers but suffered severe alpha-beta T -cell immunodeficiency .