NEW MUTATION IN EXON-12 OF THE GP91-PHOX GENE LEADING TO CYTOCHROME B-POSITIVE X-LINKED CHRONIC GRANULOMATOUS-DISEASE

We have previously reported a patient with cytochrome b-positive X-lin ked chronic granulomatous disease, Although the O-2(-) production of n eutrophils from the patient was completely defective, we presented dat a suggesting that the patient's cytochrome b was present at a normal l evel and possibly had normal spectroscopic features, Thus, to look for a mutation in the cytochrome b heavy chain (gp91-phox) gene, DNA anal ysis of gp91-phox cDNA derived from this patient was performed. As a r esult, we found that five nucleotides (1521 through 1525) within exon 12 were deleted, and a new sequence of eight nucleotides was inserted. This mutation converted Gln(507)-Lys(508)-Thr(509) into His-Ile-Trp-A la, Mismatched polymerase chain reaction showed that the mother has bo th wild and mutated alleles, confirming that this case was transmitted in an X-linked fashion. This mutation is different from those previou sly reported by others, The translocation of p47-phox and p67-phox to the membrane fraction occurred, indicating the complete formation of n icotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, We conclude that this case suggests that the structure encoded on exon 1 2 of gp91-phox is important for electron transfer. (C) 1995 by The Ame rican Society of Hematology.