X chromosome linked immunodeficiency

Abstract

Six human immunodeficiency diseases have been associated with the X chromosome by family studies. Genetic mapping with restriction fragment length polymorphisms (RFLPs) has permitted assignment of these diseases to specific loci on the X chromosome. Each of the disease entities maps to a single locus, confirming that the diagnostic criteria describe single diseases. X-linked chronic granulomatous disease and Wiskott-Aldrich syndrome map to loci on the short arm of the X chromosome; X-linked severe combined immunodeficiency, X-linked agammaglobulinemia, X-linked immunodeficiency with hyper-IgM, and X-linked lymphoproliferative syndrome map to loci on the long arm. Lyon's hypothesis predicts that these X-linked immunodeficiencies may be detectable in carriers of the diseases as a result of X chromosome inactivation of the normal disease gene. Four of the immunodeficiency diseases, X-linked agammaglobulinemia, X-linked severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and X-linked chronic granulomatous disease, affect cellular development so that carriers have a monomorphic population of immunocytes. The specific immunocyte development affected in carriers varies according to the disease. Genetic mapping of the diseases, with a collection of informative RFLPs, provides a tool that permits probability-based prenatal diagnosis. Carrier detection complements the RFLP-based genetic mapping, serving to confirm X-linkage in carriers.