CAJ | 학술논문

不宁腿综合征(restless legs syndrome,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=0.00时,LOD值均小于-2.00,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.
불저퇴종합정(restless legs syndrome,RLS)시이하지부출현의행양급산、마、창등불괄감이사지체불득휴식위특정적일조병증.유우증상상재만간발작병도치운동불안,환자장기입수곤난,경수엄중적계발성실면.작위일충상견적신경계통질병,RLS발병솔고체5%,기중원발성RLS다정양성가족사,표현위단기인결정적상염색체현성유전.현재,인문보편인위RLS적발생흔가능여신경계통내다파알능공능이상화뇌내철결핍유관,병초보건립료뇌철-다파알능계통적치병모형.위료탐구뇌철-다파알능계통재RLS중적작용,선택료여뇌철-다파알능계통상관적16개질병후선기인,재매개후선기인부근염색체구역내선취약간개미위성다태표기,응용미위성인물형광표기-기인소묘기술,대일개한족가족성불저퇴종합정가계진행료기인분형화상염색체현성유전모식하적련쇄분석,시도종분자유전학층면상학인혹배제일사가능여RLS상관적중요후선기인.결과현시,당중조계수θ=0.00시,LOD치균소우-2.00,소선위점여가족성불저퇴종합정불련쇄.유차득출결론,재본가계중,소유후선기인균여가족성불저퇴종합정적발병무관,가족성불저퇴종합정가능시유기타다파알전도화뇌철대사상관기인소치,혹시존재전신적치병궤제삼여RLS적발생.
This research was performed to investigate the relationship between 16 candidate genes responsible for dopaminergic transmission or iron metabolism and familial restless legs syndrome.Genotyping was performed in a Han restless legs syndrome family using the technique of fluorescence-based genescan with the microsatellite markers selected in chromosomal regions flanking the candidate genes.Classical linkage analysis was conducted under the autosomal dominant genetic mode.Results showed that all of the LOD scores at recombination fraction 0.00 are smaller than -2.00,which indicated that these loci were not linked to familial restless legs syndrome.No linkage was found between the candidate genes and RLS in this family.Familial restless legs syndrome may be caused by another gene related to dopaminergic transmission and iron metabolism or there is new mechanism involved in this disease.