| Co-Investigator(Kenkyū-buntansha) |
NUNOI Hiroyuki Kumamoto University, School of Med., Associate Professor, 医学部, 助教授 (50218260)
KOMIYAMA Jun Shinshu University, School of Med., Professor, 医学部, 教授 (50020798)
KITAGAWA Seiichi Osaka City University, School of Med., Professor, 医学部, 教授 (50133278)
SENDO Fujiro Yamagata University, School of Med., Professor, 医学部, 教授 (80091833)
KOBAYASHI Kunihiko Hokkaido University, School of Med., Professor, 医学部, 教授 (60091451)
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| Research Abstract |
During this study, more than 220 chronic granulomatous disease (CGD) patients in Japan have been registered. The incidence was calculated to be 4-5 in one million birth. In 120 patients examined, lesions in either subunits of the cytochrome account for about 90% of the cases and majority of defects were found in gp9l-phox, which is inherited in an X-linked fashion. We analyzed a total of 20 cases of CGD patients with gp91-phox deficiency and found that 4 missense mutations, 7 nonesense mutations, 2 insertion, 4 deletions and 2 splice site mutations. One interesting case found was a patient with normal expression of the superoxide generating system only in eosinophils. In all cases of p47-phox deficiency, the defect was identified to be a GT (or TG)-dinucleotide deletion at bases 75/76 (or 74/75, respectively) in the coding sequence for the protein probably due to a inverted repeat sequence around an intron-exon junction. About p67 deficiency, a homologous AG dinucleotide insertion in one patient and an inflame deletion between 694 to 879, which correspond to entire sequence of exon 8 and 9. For gene therapy of the patients, two sets of vectors were studied, one was a very high titer of MFGS-91 developed in US and the other was a drug-selectable bicistronic vector that would give higher therapeutic benefit in future. Molecular mechanism of activation of the superoxide generating system was also investigated. As a novel type of phagocyte disorders, a patient who had mutant beta-actin was found and its details were analyzed. A new type of GPI anchored protein which regulate leukocyte extravasation was found and characterized.
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