Application of carrier testing to genetic counseling for X-linked agammaglobulinemia.

摘要: Bruton X-linked agammaglobulinemia (XLA) is a phenotypically recessive genetic disorder of B lymphocyte development. Female carriers XLA, although asymptomatic, have characteristic cell lineage-specific skewing the pattern X inactivation. Skewing apparently results from defective growth and maturation precursors bearing mutant active chromosome. In this study, carrier status was tested in 58 women 22 families referred with history agammaglobulinemia. Primary analysis to examine patterns inactivation CD19+ peripheral blood cells (B lymphocytes) conducted using quantitative PCR at androgen-receptor locus. Obligate XLA demonstrated > 95% but not CD19- cells. Carrier for mothers isolated affected males could be assessed 10 11 families: 7 showed skewing, 3 did not. Five were found six which there no living males. Among all those tested, one individual's considered indeterminate five noninformative test. Results obtained by test congruent linkage (where applicable) RFLPs DXS178 DXS94 two newly developed polymorphic microsatellite markers, DXS178CA DXS101AAT. Refinements techniques primary testing mapping now make possible an ordered approach diagnosis, prenatal counseling.