부산대학교 도서관

Chronic granulomatous disease is an inherited disorder in which phagocytes lack a functional NADPH oxidase and so cannot generate superoxide anions (O). The most common form is caused by mutations inCYBBencoding gp91phox, the heavy chain of flavocytochromeb558 (XCGD). We investigated 11 male patients and their families suspected of suffering from X-linked CGD. These XCGD patients were classified as having different variants (X910, X91- or X91+) according to their cytochromeb558 expression and NADPH oxidase activity. Nine patients had X910 CGD, one had X91- CGD and one had X91+ CGD. Six mutations inCYBBwere novel. Of the four new X910 CGD cases, three were point mutations: G65A in exon 2, G387T in exon 5 and G970T in exon 9, leading to premature stop codons at positions Try18, Try125 and Glu320, respectively, in gp91phox. One case of X910 CGD originated from a new 1005G deletion detected in exon 9. Surprisingly, four nonsense mutations in exon 5 led to the generation of two mRNAs, one with a normal size containing the mutation and the other in which exon 5 had been spliced. A novel X91- CGD case with low gp91phoxexpression was diagnosed. It was caused by an 11-bp deletion in the linking region between exon 12 and intron 12, activating a new cryptic site. Finally, a new X91+ CGD case was detected, characterized by a missense mutation Leu505Arg in the potential NADPH-binding site of gp91phox. No clear correlation between the severity of the clinical symptoms and the sub-type of XCGD could be established. [ABSTRACT FROM AUTHOR]