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不宁腿综合征 (restlesslegssyndrome,RLS)是以下肢部出现蚁行样及酸、麻、胀等不适感而使肢体不得休息为特征的一组病症。由于症状常在晚间发作并导致运动不安 ,患者长期入睡困难 ,经受严重的继发性失眠。作为一种常见的神经系统疾病 ,RLS发病率高达 5 % ,其中原发性RLS多呈阳性家族史 ,表现为单基因决定的常染色体显性遗传。现在 ,人们普遍认为RLS的发生很可能与神经系统内多巴胺能功能异常和脑内铁缺乏有关 ,并初步建立了脑铁 多巴胺能系统的致病模型。为了探求脑铁 多巴胺能系统在RLS中的作用 ,选择了与脑铁 多巴胺能系统相关的 16个疾病候选基因 ,在每个候选基因附近染色体区域内选取若干个微卫星多态标记 ,应用微卫星引物荧光标记 基因扫描技术 ,对一个汉族家族性不宁腿综合征家系进行了基因分型和常染色体显性遗传模式下的连锁分析 ,试图从分子遗传学层面上确认或排除一些可能与RLS相关的重要候选基因。结果显示 ,当重组系数θ =0 0 0时 ,LOD值均小于 - 2 0 0 ,所选位点与家族性不宁腿综合征不连锁。由此得出结论 ,在本家系中 ,所有候选基因均与家族性不宁腿综合征的发病无关 ,家族性不宁腿综合征可能是由其他多巴胺传导和脑铁代谢相关基因所致 ,或是存在全新的致病机制参与RLS的发生
Restless leg syndrome (restlesslegssyndrome, RLS) is a set of conditions characterized by the fact that the limbs may not rest with the ants in the lower extremities and the discomfort such as acid, hemp and swelling. Because symptoms often attack in the evening and lead to exercise disorders, patients with long-term difficulty falling asleep, suffering from severe secondary insomnia. As a common neurological disease, the incidence of RLS is as high as 5%. Among them, the primary RLS is mostly positive family history, showing single gene-determined autosomal dominant inheritance. Now, it is generally believed that the occurrence of RLS is likely to be associated with abnormal dopaminergic neurons and brain iron deficiency, and initially established a model of brain dopaminergic system pathogenic. In order to explore the role of brain dopaminergic system in RLS, 16 disease candidate genes related to the brain dopaminergic system were selected. A number of microsatellite polymorphic markers were selected in the chromosome region near each candidate gene. Microsatellite Primer fluorescent marker gene scanning technology, a familial Restless Leg Syndrome family of Han Chinese genotypes and autosomal dominant inheritance pattern of linkage analysis, trying to confirm or exclude from the molecular genetic level may be related to RLS Important candidate gene. The results showed that when the recombination coefficient θ = 0 0 0, the LOD values were less than -200, and the selected loci did not link with familial restless legs syndrome. This concludes that in this pedigree, all candidate genes are unrelated to the onset of familial restless legs syndrome, familial restless legs syndrome may be caused by other dopamine-mediated and brain iron metabolism related genes or There is a new pathogenic mechanism involved in the occurrence of RLS