title: Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation.
abstract: We used a recently developed strategy to analyze patterns of X-chromosome inactivation in human cell populations in order to study female members of families with X-linked agammaglobulinemia--i.e., to detect the carrier state and to test the hypothesis that the disorder results from a defect intrinsic in the development of B cells. According to this strategy, recombinant-DNA probes simultaneously detect restriction-fragment-length polymorphisms and patterns of methylation of X-chromosome genes. Random X-inactivation patterns were observed in isolated peripheral-blood granulocytes, T lymphocytes, and B lymphocytes of women who were not carriers. In contrast, one of the two X chromosomes was preferentially active in the peripheral B cells, but not the T cells or granulocytes, of three carriers of the disorder. This observation strongly supports the hypothesis that X-linked agammaglobulinemia results from an intrinsic defect in B-cell development. Moreover, the analysis described here can be used for direct identification of carriers in families with this disease.
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics*; D001402:B-Lymphocytes / Q000032:analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008745:Methylation; D012150:Polymorphism, Restriction Fragment Length; D013601:T-Lymphocytes / Q000032:analysis; D014960:X Chromosome