Microsatellite linkage analysis for determination of disease locus of Moyamoya disease.

我们对6个家族性烟雾病家系和24对患病同胞进行了微卫星连锁分析，以确定其发病位点。为了缩小搜索区域，我们集中在染色体17上，其中偶尔与烟雾病相关的神经纤维瘤病I型基因位于染色体17上，并且在染色体19上，家族性偏瘫性偏头痛（FHM）和CADASIL基因位于染色体19上。每个个体的PCR扩增的微卫星标记在自动测序仪上用GeneScan分析软件进行分析。在染色体17 q25-ter区域发现了一个正连锁，在标记D17 S939处的两点连锁分析显示最大LOD值为3.11。在一个偏头痛家系中，与19 p13染色体上的FHM/CADASIL基因相邻的标记未发现连锁，而与17染色体上的FHM/CADASIL基因相邻的标记未发现连锁，提示19 p染色体上存在Moyamoya病的独立基因。

We have applied microsatellite linkage analysis on a total of 6 pedigrees and24 affected sib-pairs of familial Moyamoya disease in order to determine the disease locus. To narrow search regions, we focused on chromosome 17 where the gene for neurofibromatosis type I that occasionally associates with Moyamoya disease is located, and on chromosome 19 where the gene for familial hemiplegic migraine (FHM) and CADASIL is located. PCR amplified microsatellite markers of each individual were analysed on an automated sequencer with the GeneScan analysis software. A positive linkage was found on chromosome 17q25-ter region, demonstrating a maximum LOD score of 3.11 by the two-point linkage analysis at a marker D17S939. Affected pedigree member method also showed p value less than 10-5 for 4 markers around D17S939.In one pedigree in which patients presented with migraine, linkage was not observed with markers adjacent to FHM/CADASIL genes on chromosome 19pl3 but not with chromosome 17, suggesting the presence of distinct gene for Moyamoya disease on chromosome l9p.