RFLP and deletion analysis for X-linked chronic granulomatous disease using the cDNA probe: potential for improved prenatal diagnosis and carrier determination.

The molecular basis of X-linked chronic granulomatous disease (X-CGD) has recently been elucidated and the defective gene identified and isolated. Two restriction fragment-length polymorphisms have been identified using the X-CGD cDNA probe. We have analyzed eight families with X-CGD and seven normal, unrelated females and have demonstrated that these polymorphisms are not in linkage disequilibrium. This should increase to approximately 50% the proportion of families to whom first-trimester prenatal diagnosis can be offered. Unambiguous determination of carrier status in related females in informative families will also be possible. In addition, we have identified an apparently unique small deletion in the X-CGD gene in a family affected by this disease, members of which are not informative for either polymorphism. This will allow prenatal diagnosis and carrier determination in this family.