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

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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