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The majority of known female carriers of X-linked chronic granulomatous disease (X-CGD), a deficiency of the 91kd phox (phagocyte oxidase) subunit and the most common genetic subtype of CGD, are not informative for the intragenic restriction fragment length polymorphisms (RFLPs) described to date. Here I report the isolation and characterization of two polymorphic (CA/GT)n repeats that lie within the X-CGD gene. Analysis of DNA derived from over 100 individuals shows both markers to be highly polymorphic (11 alleles each) with a resultant high proportion of heterozygosity in females. Several kindreds affected by X-CGD were studied and the (CA/GT)n length polymorphisms were shown to segregate with the clinical syndrome or biochemical carrier status. The technique was prospectively applied to several kindreds containing a carrier mother and an affected child. In a case where a male fetus was scheduled to be terminated, the fetus was shown to carry the unaffected allele, and consequently the pregnancy was carried to term. The infant was demonstrated to be unaffected. Advantages of this approach are the high degree of informativity in a multiple allele system, the rapidly of the technical analysis (hours), the minimal amount of DNA required (nanogram), the ability to transport diagnostic samples and therefore the ability to use this method early in pregnancy on a chorionic villus biopsy sample for prenatal diagnosis.