Alpha/beta T-Cell Lymphopenia With Gamma/delta T-Cell Expansion, Severe Cytomegalovirus Infection, And Autoimmunity

A number sign (#) is used with this entry because alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus (CMV) infection, and autoimmunity is caused by mutations in the RAG1 gene (179615). Mutations in the RAG1 gene also cause T cell-negative, B cell-negative, natural killer (NK) cell-positive severe combined immunodeficiency (SCID; 601457) and Omenn syndrome (603554).

Clinical Features

De Villartay et al. (2005) reported 4 unrelated infants born to first cousins of Algerian, Moroccan, Lebanese, and Turkish origin who presented with persistent CMV infection before 1 year of age. In 3 patients, CMV infection was associated with autoantibodies to red cells, causing anemia. Autoantibodies to neutrophils were present in 1 of these patients, and antinuclear autoantibodies were present in 2 of these patients. The numbers of lymphocytes and lymphocyte subsets (i.e., T, B, and NK cells) were normal in 3 patients and low in 1 patient, but the ratio of TCR-alpha (see 186880)/beta (see 186930) to TCR-gamma (see 186970)/delta (see 186810) T cells was nearly inverse the normal ratio in all 4 patients.

Molecular Genetics

De Villartay et al. (2005) identified homozygous mutations in the RAG1 gene (e.g., 179615.0017) in all 4 patients they reported with alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe CMV infection, and autoimmunity. They concluded that hypomorphic RAG1 mutations result in residual RAG1 activity and are compatible with the presence of both B and T lymphocytes. De Villartay et al. (2005) suggested that the immunologic phenotypes associated with RAG1 mutations are dependent on both genetic background and the microbial environment.