Evidence for further genetic locus heterogeneity and confirmation of RLS-1 in restless legs syndrome
Evidence for further genetic locus heterogeneity and confirmation of RLS-1 in restless legs syndrome
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DOI：
10.1002/mds.20627
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发表时间：
2006-01-01
影响因子：
8.6
通讯作者：
Muller-Myhsok, B
中科院分区：
文献类型：
--
作者：
Winkelmann, J;Lichtner, P;Muller-Myhsok, B
不宁腿综合征（RLS; MIM 102300）是一种常见的神经系统疾病，其特征是感觉迟钝和移动下肢的冲动。症状主要发生在休息时，晚上，并随着运动而改善。在12 q、14 q和9 p染色体上发现3个RLS基因座（RLS-1、RLS-2和RLS-3），分别为隐性遗传（RLS-1）和常染色体显性遗传（RLS-2、RLS-3）。这些基因座对这种疾病的总体贡献尚不清楚。为了评估这些位点的意义，我们调查了12个RLS家族可能与这些染色体区域的连锁。使用26个多态性微卫星标记（染色体12：7;染色体14：7，染色体9：12）在70个受影响的家庭成员中进行基因分型。连锁分析是使用在原始研究中应用的已发表的参数进行的（12号染色体：q = 0.25，f（0）= 0.005，f（1）= 0.005，f（2）= 0.8; 14号染色体：q = 0.003，f（0）= 0.005，f（1）= f（2）= 0.95; 9号染色体：q = 0.001，f（0）= 0.005，f（1）= f（2）= 0.95;仅受影响个体）。此外，还进行了传递不平衡检验（TDT）。我们使用TDT发现了12号染色体上连锁的证据。12个家系中有1个排除了与RLS-2和RLS-3的连锁。这支持了RLS-1的存在，并为RLS进一步的遗传位点异质性的可能性提供了证据。需要对其他RLS家族进行调查以确认已知的基因座，进一步的全基因组连锁分析有可能鉴定其他RLS基因座。(C)2005年，任上海市人民政府副市长。
Restless legs syndrome (RLS; MIM 102300) is a common neurological disorder characterized by dysesthesias and an urge to move the lower limbs. The symptoms predominantly occur at rest, in the evening, and improve with movement. There is a high familial aggregation but gene mutations have not yet been found. Three loci for RLS on chromosomes 12q, 14q, and 9p (RLS-1, RLS-2, and RLS-3) have been reported with a recessive (RLS-1) and autosomal dominant (RLS-2, RLS-3) mode of inheritance, respectively. The overall contribution of these loci to this disorder is not known. To evaluate the significance of these loci, we investigated 12 RLS families for possible linkage to these chromosomal regions. Genotyping was carried out in 70 affected family members using 26 polymorphic microsatellite markers (chromosome 12: 7; chromosome 14: 7, chromosome 9: 12). Linkage analysis was carried out using the published parameters applied in the original studies (chromosome 12: q = 0.25, f(0) = 0.005, f(1) = 0.005, f(2) = 0.8; chromosome 14: q = 0.003, f(0) = 0.005, f(1) = f(2) = 0.95; chromosome 9: q = 0.001, f(0) = 0.005, f(1) = f(2) = 0.95; affected individuals only). In addition, transmission disequilibrium test (TDT) analyses were done. We found evidence for linkage on chromosome 12 using the TDT. Linkage to RLS-2 and RLS-3 was excluded in 1 of 12 families. This supports the existence of RLS-1 and provides evidence for the likelihood of further genetic locus heterogeneity of RLS. Investigations in additional RLS families are required to confirm the known loci and further genome wide linkage analyses have the potential to identify additional RLS loci. (C) 2005 Movement Disorder Society.