SOMATIC TRIPLE MOSAICISM IN A CARRIER OF X-LINKED CHRONIC GRANULOMATOUS-DISEASE

The X-linked form of chronic granulomatous disease (CGD) is caused by mutations in the CYBB gene, which encodes the 91-kD subunit of the fla vocytochrome b(558), a component of the superoxide-generating nicotina mide adenine dinucleotide phosphate (NADPH) oxidase in phagocytic leuk ocytes, Mutations in this gene are very heterogeneous and often unique for one family, Here we report on a family with two patients (brother s), one with a 3-kb deletion comprising exon 5 and the other with a 3. 5-kb deletion comprising exons 6 and 7 of the CYBB gene, Sequence anal ysis of polymerase chain reaction (PCR)-amplified genomic DNA proved t hese deletions to be overlapping for 35 bp, Analysis by restriction fr agment length polymorphism of genomic DNA from the mother's leukocytes showed her to be a carrier of both deletions in addition to the norma l CYBB sequence, This triple somatic mosaicism was confirmed with PCR- amplified genomic and complementary DNA, The presence of the normal CY BB gene in the mother was also proven by the finding of normal superox ide-generating neutrophils in addition to cells lacking this ability. Triple X syndrome was excluded. These findings suggest that the mutati ons are the result of an event in early embryogenesis of the mother, p ossibly involving a mechanism like sister chromatid exchange. (C) 1998 by The American Society of Hematology.