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

目的与背景：认为家族性烟雾病与某些遗传因素密切相关。先前的微卫星分析表明，相关基因可能位于染色体3、8、12和17上。然而，致病基因尚未被确定。本研究旨在鉴定位于17825位点的相关基因。此外，还研究了临床预期和三联体重复的存在，并测定了烟雾病患者脑脊液的基本FGF和HGF。方法与结果：从17825染色体D17S785-D17S836的9-cM区域共鉴定的65个基因中，选择9个基因作为候选基因，对1例家族性烟雾病家系DNA样本进行序列分析，单倍型分析显示与该区域具有完全连锁关系。此外，我们试图利用生物信息学技术，从总共2,100个表达序列标签（EST）序列中识别出尚未被发现但可能与该疾病更相关的候选基因。结果表明，序列分析未发现9个基因发生突变。我们也无法通过EST分析确定新的候选基因。对141例烟雾病患者进行了临床预测研究。本分析显示家族性烟雾病有明显的临床预见性。17g25位点未发现三联体重复。术中取患者脑脊液。控制值以无症状脑动脉瘤患者及其他缺血性脑血管病患者为研究对象。结果表明，与对照组相比，烟雾病患者脑脊液中碱性FGF和HGF值较高。结论：在家族性烟雾病患者中观察到的临床预测提示，烟雾病患者的某些基因可能存在三联体重复序列。为了阐明烟雾病的发病机制，有必要采用其他方法进行进一步的研究。然而，我们的结果表明，包括碱性fgf和HGF在内的一些细胞因子的高水平表明，一些与这些细胞因子相关的基因异常与烟雾病的发病密切相关。少

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