MOLECULAR GENETIC ANALYSIS OF CHRONIC GRANULOMATOUS DISEASE.

慢性肉芽肿性疾病的分子遗传学分析。

• 批准号: 04404046
• 负责人: MATSUMOTO Shuzo
• 金额: $ 7.04万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404046/
• 关键词: CHRONIC GRANULOMATOUS DISEASE; MOLECULAR GENETIC ANALYSIS; 好中球チトクローム重鎖遺伝子; 遺伝子学的解析; 点突然変異

We have investigated molecular genetic analysis in patients with chronic granulomatous disease (CGD) during 1992-1993. We had totally 21 patients from 20 different families to study, in which we could determine 17 patients from 16 families as an X-linked type CGD.We have shown that 4 patients revealed to have abnormal restriction length patterns on Southern blot analysis using the CYBB cDNA as a probe (Pediatr Res 31 : 516-519, 1992). The abnormal patterns were different from one another, which suggested genetic heterogeneity in X-CGD.We further studied to find the mutations of the CYBB gene in 7 patients with X-CGD (Eur J Pediatr 152 : 469-472, 1993 ; Eur J Haematol in press ; submitted for publication). The mutations found were quite various, which were consistent with the results of Southern blot analysis. We applied these results to the diagnosis of the carrier state in the patients' sisters. The results clearly demonstrated that three sisters were carriers of the disease, and one was not a carrier.We made EBV lymphoblastoid cell lines from the patients and healthy controls. Using the cell lines, we established the system to detect superoxide production in vitro by chemiluminescence (Submitted for publication). This system would be useful for the gene transduction studies to restore the phagocyte function of the CGD patients.

我们研究了1992 - 1993年期间慢性肉芽肿（CGD）患者的分子遗传分析。我们完全有来自20个不同家庭的21名患者进行研究，其中我们可以确定16个家庭的17例患者为X连锁型CGD。我们表明，使用Cybb cDNA作为探针，在Southern印迹分析上有4例患者在Southern印迹分析上具有异常的限制长度模式（PediatiTr Res 31：516-519，1992，1992，1992，1992）。异常模式彼此不同，这表明X-CGD中的遗传异质性。我们进一步研究了7例X-CGD患者的Cybb基因的突变（Eur J Pediatr 152：469-472，1993; Eur J Haematol in Press in Press;提交出版）。发现的突变非常不同，这与Southern印迹分析的结果一致。我们将这些结果应用于患者姐妹中载体状态的诊断。结果清楚地表明，三个姐妹是该疾病的携带者，一个不是携带者。我们使患者的EBV淋巴细胞细胞系和健康对照组。使用细胞系，我们通过化学发光（提交出版）建立了该系统以在体外检测超氧化物的产生。该系统对于基因转导研究很有用，可以恢复CGD患者的吞噬细胞功能。

项目成果

T Ariga, A Hoshioka, S Matsumoto et al.: "A denovo mutation in the C1 inhibitor gene in a case of sporadic hereditary angio neurotic edema." Clin Immunol Immunopathol. 69. 103-106 (1993)

T Ariga、A Hoshioka、S Matsumoto 等人：“散发性遗传性血管神经性水肿病例中 C1 抑制剂基因的新生突变。”

TAFASHI ARIGA etal.: "Genetic beterogeneity in Patients weth X liulacd recessiue chronic gionu lomatous digeaoa" Pediatric Regearch. 31. 516-519 (1992)

TAFASHI ARIGA 等人：“X liulacd 隐性慢性 gionu lomatous digeaoa 患者的遗传异质性”儿科治疗。

T Ariga, Y Sakiyama, S Matsumoto et al.: "Genetic heterogeneity in patients with X-linked resessive chronic granulomatous disease." Pediatric Research. 31. 516-519 (1992)

T Ariga、Y Sakiyama、S Matsumoto 等人：“X 连锁隐性慢性肉芽肿病患者的遗传异质性。”

T Ariga,Y Sakiyama,S Matsumoto et al.: "Molecular genetic stusies of two families with X-linked chronic granulomatous disese:Mutation analysis and definitive determination of carrier status in patiets' sisters." Eur J Heamatol. (in press).

T Ariga、Y Sakiyama、S Matsumoto 等人：“两个 X 连锁慢性肉芽肿病家族的分子遗传学研究：突变分析和患者姐妹携带者状态的明确确定。”

T Ariga,Y Sakiyama,S Matsumoto et al.: "Molecular genetic stusies of two families with X-linked chronic granulomatous disese:Mutation analysis and definitive determination of carrier status in patiets'sisters." Eur J Heamatol. in press.

T Ariga、Y Sakiyama、S Matsumoto 等人：“两个 X 连锁慢性肉芽肿病家族的分子遗传学研究：突变分析和患者姐妹携带者状态的明确确定。”