Genetic diagnosis for twelve cases of X-linked chronic granulomatous disease

To explore the value of genetic diagnosis for X-linked chronic granulomatous disease (X-CGD), we analyzed the variation of CYBB gene in twelve cases of X-CGD. Clinical features and laboratory data of patients with X-CGD showed that all of patients suffered from recurrent infections. Nitroblue tetrazolium (NBT) test and flow cytometry-DHR assay were used for evaluating neutrophil function. The NBT results before and after PMA and LPS stimulation were markedly lower (0-6% ); the neutrophil oxidative index in 11 X-CGD patients tested by Flow cytometry-DHR assay was 1-2, significantly lower than healthy controls (100), diagnosed as XCGD. By direct PCR or RT-PCR sequencing, the CYBB gene from the patients and their family members were analyzed. The Genomic DNA from fetus amniotic fluid cells, whose mother was a carrier of mutant CYBB gene, was used to sequencing CYBB gene. By sequence analysis, 1 patient had normal CYBB gene and 11 patients were found with CYBB gene mutations, including four deletion mutations, four splicing errors, two nonsense mutations, and a missense mutation. And seven of those were novel mutations. In the mothers of the 11 mutated patients, 9 mothers are carriers of gene mutation, 1 mother is indefinite, and a mother is not a carrier of gene mutation. These results mean that genetic diagnosis is useful for identification of X-CGD patients and represents an important tool for carrier detection as well as prenatal diagnosis. Furthermore, genetic diagnosis also provides the evidences for hematopoietic stem cell transplantation treatment in XCGD patients.