A novel locus for restless legs syndrome maps to chromosome 19p in an Irish pedigree
A novel locus for restless legs syndrome maps to chromosome 19p in an Irish pedigree
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DOI：
10.1007/s10048-012-0317-x
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发表时间：
2012-05-01
期刊：
影响因子：
2.2
通讯作者：
Hand, Collette K.
中科院分区：
文献类型：
--
作者：
Skehan, Evelyn B.;Abdulrahim, Manal M. A.;Hand, Collette K.
不宁腿综合征（RLS）是一种常见的睡眠相关运动障碍。症状遵循昼夜节律模式，在晚上或夜间恶化，导致睡眠中断和白天嗜睡。家族性RLS已被描述，通常表现为常染色体显性遗传模式。迄今为止，连锁分析已确定了9个RLS位点，但没有具体的致病基因已被报道。关联作图突出了另外四个感兴趣的基因组领域。我们进行了全基因组连锁分析，在爱尔兰常染色体显性遗传的RLS家系与11个受影响的成员。在染色体19 p上发现了一系列微卫星标记的显着连锁，标记D19S878在θ = 0.0处的最大两点LOD得分为3.59。通过单倍型分析鉴定的突变事件在染色体19p13.3上定义了6.57 cM的遗传区域，对应于2.5 Mb的间隔。这项研究提供了一种新型RLS基因座的证据，并进一步证明RLS是一种遗传异质性疾病。
Restless legs syndrome (RLS) is a common, sleep-related movement disorder. The symptoms follow a circadian pattern, worsening in the evening or night, leading to sleep disruption and daytime somnolence. Familial forms of RLS have been described and usually display an autosomal dominant pattern of inheritance. To date, linkage analysis has identified nine RLS loci, but no specific causative gene has been reported. Association mapping has highlighted a further four genomic areas of interest. We have conducted a genome-wide linkage analysis in an Irish autosomal dominant RLS pedigree with 11 affected members. Significant linkage was found on chromosome 19p for a series of microsatellite markers, with a maximum two-point LOD score of 3.59 at theta = 0.0 for marker D19S878. Recombination events, identified by haplotype analysis, define a genetic region of 6.57 cM on chromosome 19p13.3, corresponding to an interval of 2.5 Mb. This study provides evidence of a novel RLS locus and provides further evidence that RLS is a genetically heterogenous disorder.