Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation

N Engl J Med. 1987 Feb 19;316(8):427-31. doi: 10.1056/NEJM198702193160802.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agammaglobulinemia / genetics*
  • B-Lymphocytes / analysis
  • Dosage Compensation, Genetic*
  • Female
  • Genetic Carrier Screening / methods*
  • Genetic Linkage
  • Humans
  • Male
  • Methylation
  • Polymorphism, Restriction Fragment Length
  • T-Lymphocytes / analysis
  • X Chromosome