Carrier detection in typical and atypical X-linked agammaglobulinemia.
We have recently demonstrated that B cells from obligate carriers of typical X-linked agammaglobulinemia (XLA) exhibit nonrandom X chromosome inactivation. The active X is always the X that does not carry the gene defect. To determine if this were also true in carriers of atypical XLA and to provide carrier detection for all women at risk of being carriers of XLA, we developed a technique that permits analysis of X chromosome inactivation in cells from any woman. This technique combines the production of somatic cell hybrids that selectively retain the active X chromosome with the use of X-linked restriction fragment length polymorphisms that permit the distinction of the two X chromosomes. Three obligate carriers of typical XLA and four women whose sons might be considered to have atypical or sporadic XLA were studied. B cell hybrids from all seven women demonstrated exclusive use a single X as the active X. In addition, B cell hybrids from four of eight women at 25% or 50% risk of being carriers exhibited nonrandom X chromosome inactivation, indicating that these women were also carriers of X-linked forms of hypogammaglobulinemia. These results illustrate a technique that can be used both to help define XLA and to provide carrier detection for all women at risk of being carriers of this disorder.
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; D006822:Hybrid Cells / Q000032:analysis; D008126:Lod Score; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D014960:X Chromosome / Q000032:analysis*