X chromosome inactivation patterns in obligate carriers of X-linked lymphoproliferative syndrome

To determine whether the gene defect that causes X-linked lymphoproliferative syndrome (XLP) results in a selective disadvantage in proliferation or survival of leukocytes, we analyzed X chromosome inactivation patterns in neutrophils, T cells, and B cells from two unrelated obligate carriers of XLP. Analysis of DNA methylation patterns and production of somatic cell hybrids demonstrated that all three cell lines from both women exhibited normal, random X chromosome inactivation. These findings indicate that the XLP gene defect does not result in a global defect in proliferation or survival of T cells or B cells. It remains possible that a subset of T or B cells or natural killer cells may be selectively affected. It is also possible that the gene defect alters function but not proliferation or survival of T or B cells.