Investigation of causative gene of familial occurrence of idiopathic occlusion of Willis ring

特发性Willis环闭塞家族性致病基因的调查

• 批准号: 14370441
• 负责人: HOUKIN Kiyohiro
• 金额: $ 8.7万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370441/
• 关键词: Moyamoya disease; microsatelite analysis; familial occurrence; angiogenesis

Purpose and Background:It is estimated that some genetic factors are closely related to the familial moyamoya disease. Previous microsatellite analysis has suggested that related genes may be located on chromosomes 3,8,12 and 17. However, the responsible gene has not been identified yet. This study aimed to identify the responsible genes that are located in the 17825 locus. In addition, clinical anticipation and the presence of triplet repeat was investigated and the basic FGF and HGF of the cerebrospinal fluid of moyamoya patients were measured.Methods and Results:Considering the function, we selected nine genes as candidates from a total of 65 genes identified in the 9-cM region of D17S785-D17S836 in chromosome 17825, and performed sequence analysis on the DNA samples obtained from a pedigree of familial moyamoya disease, which showed a complete linkage to the region by a haplotype analysis. Also, we attempted to identify candidate genes that have not been known but might be function … More ally relevant to the disease among a total of 2,100 expressed sequence tag (EST) sequences using bioinformatics techniques. As results, the sequence analysis could detect no mutation in the nine genes. Nor could we identify a novel candidate gene by the EST analysis.Clinical anticipation study was done based on 141 cases with moyamoya disease. This analysis revealed that apparent clinical anticipation was observed in familial moyamoya disease. No triplet repeat was found in 17g25 locus.Cerebrospinal fluid was obtained from the patients during surgery. Control value was measured using asymptomatic cerebral aneurysm patients and other ischemic cerebrovascular disease. As results, high value of basic FGF and HGF was seen in the cerebrospinal fluid of moyamoya patients compared to the control group.Conclusions:Clinical anticipation observed in familial moyamoya patients suggests that some triplet repeat may located in some gene in moyamoya disease. Further studies using alternative approaches are warranted to clarify the pathogenesis of moyamoya disease. However, our results of high level of some cytokines including basicFGF and HGF suggests that some gene abnormality related to these cytokines are closely involved the pathogenesis of moyamoya disease. Less

目的和背景：家族性烟雾病与遗传因素密切相关。先前的微卫星分析表明，相关基因可能位于第3、8、12和17号染色体上。然而，负责的基因尚未被确定。本研究旨在确定位于17825位点的相关基因。此外，临床预期和存在的三重重复序列进行了调查和基本的成纤维细胞生长因子和肝细胞生长因子的烟雾病患者的脑脊液measured.Methods和结果：考虑到功能，我们选择了9个基因作为候选人，共65个基因中确定的9-cM区域的D17 S785-D17 S836在染色体17825，并进行序列分析的DNA样本从一个家系的家族性烟雾病，这表明一个完整的连锁区域的单倍型分析。此外，我们试图确定候选基因，尚未知道，但可能是功能 ...更多信息 利用生物信息学技术，在总共2，100个表达序列标签（EST）序列中筛选出与疾病相关的基因。结果表明，序列分析在9个基因中未检测到突变。我们也无法通过EST分析找到新的候选基因。我们对141例烟雾病患者进行了临床预测研究。本分析显示，在家族性烟雾病中观察到明显的临床预期。在17 g25位点未发现三联重复。对照值采用无症状脑动脉瘤患者和其他缺血性脑血管病患者测量。作为结果，碱性成纤维细胞生长因子和肝细胞生长因子的高值被认为是在烟雾病患者的脑脊液中相比，对照组。结论：在家族性烟雾病患者中观察到的临床预期表明，一些三联重复序列可能位于烟雾病的某些基因。使用替代方法的进一步研究是必要的，以澄清烟雾病的发病机制。然而，我们的研究结果表明，一些细胞因子，包括碱性成纤维细胞生长因子和肝细胞生长因子的高水平，这些细胞因子相关的基因异常密切参与烟雾病的发病机制。少

项目成果

How does angiogenesis develop in pediatric moyamoya disease after surgery? A prospective study with MR angiography

• DOI: 10.1007/s00381-004-0971-x
• 发表时间: 2004-10-01
• 期刊: CHILDS NERVOUS SYSTEM
• 影响因子: 1.4
• 作者: Houkin, K;Nakayama, N;Nonaka, T
• 通讯作者: Nonaka, T

乳幼児もやもや病の臨床像

婴儿烟雾病的临床特点

• 发表时间: 2003
• 期刊: 脳神経外科 31
• 作者: 黒田 敏

Source localization of the re-build up phenomenon in pediatric moyamoya disease-a dipole distribution analysis using MEG and SPECT

小儿烟雾病重建现象的来源定位——利用MEG和SPECT进行偶极分布分析

• 发表时间: 2003
• 期刊: Childs Nervous System 19
• 作者: Setoguchi K;Misaki Y;Kawahata K;Shimada K;Juji T;Tanaka S;Oda H;Shukunami C;Nishizaki Y;Hiraki Y;Yamamoto K.;Qiao F
• 通讯作者: Qiao F

脳神経外科学I改訂9版(太田富雄, 松谷雅生編集)

神经外科Ⅰ，第9修订版（太田富雄、松谷正夫主编）

• 发表时间: 2004
• 作者: 宝金清博

中山 若樹, 宝金 清博, 黒田 敏: "MRAにより病期分類"厚生省もやもや病研究班平成14年度報告書. (印刷中). (2003)

Wakaki Nakayama、Kiyohiro Hokin、Satoshi Kuroda：“MRA 分期”卫生和福利部烟雾病研究小组 2002 年报告（2003 年）。