DETERMINING THE GENETICS OF THE RESTLESS LEGS SYNDROME

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。不宁腿综合症(RLS)是一种常见的睡眠障碍，影响约5%的人口。它的特点是四肢，通常是腿部有阵发性的痛苦感觉，通过受影响的肢体的运动来缓解。它通常是渐进性的，发病年龄各不相同，但对老年人来说变得更加常见和更令人痛苦。患有严重RLS的人通常很难启动和维持睡眠，并经历严重的、慢性的、致残的睡眠剥夺。这项研究的具体目的是：(1)使用直接访谈方法评估患有RLS的130名先证者的所有一级和二级亲属中RLS的存在，并将这些比率与用相同方法评估的对照样本中发现的RLS进行比较；(2)检验存在独特的早发性RLS家族性亚型的假设，并确定定义这种群体的最佳发病年龄；以及(3)通过对RLS样本中1700名预测的家庭成员的诊断数据的分离分析，推断最可能的遗传模式，并分别对早发性和晚发性RLS先证者进行这项分析。到目前为止，我们已经研究了87个RLS先证者和39个对照先证者标准完整的家系。我们目前正在采访先证者的家庭成员以及与其分享亲生子女的个人(S)。正在使用经过验证的RLS结构化诊断电话访谈通过电话进行访谈。到目前为止，我们已经采访了763名符合条件的和可用的家庭成员(RLS先证者的一级和二级亲属，对照先证者先证者的一级亲属，以及先证者子女的其他父母)。在完成的78个家庭中(50个RLS先证者家庭；28个对照先证者家庭)，我们招募了受访的RLS先证者和对照先证者的家庭成员进行血检、三天活动仪监测和临床访谈，以确认电话诊断。78个家庭已经完成并进行了分析，其中50个家庭来自RLS先证者。初步结果显示，在特发性RLS先证者的家庭成员中，RLS的频率很高。此外，家庭成员中RLS的频率似乎受到RLS先证者发病年龄的影响，如果先证者有早发性RLS，则受影响的亲属比例较高。我们还发布了自上次续签以来约翰霍普金斯结构化诊断电话访谈(TDI)的有效性报告。我们的结论是，TDI是诊断RLS的可靠、敏感和特异的工具，当有经验的采访者使用时。在接下来的一年里，我们将继续寻找合适的先驱，并使用TDI采访家庭成员。我们将继续收集血样、计量仪数据，并从已完成家庭内的受访亲属那里进行面对面的临床访谈。我们将能够在明年内至少对RLS先证者家庭进行隔离分析，因为我们预计在这段时间内将有70到80个家庭完成。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Restless Legs Syndrome (RLS) is a common sleep disorder affecting about 5% of the population. It is characterized by episodes of distressing sensations in the limbs, generally the legs, that are relieved by movement of the affected extremity. It is generally progressive, with various ages of onset, but becoming both more common and more distressing for older adults. Individuals with severe RLS usually have great difficulty initiating and maintaining sleep, and experience severe, chronic, disabling sleep deprivation. The specific aims of this study are: (1) to use direct interview methods for assessing the presence of RLS in all first- and second-degree relatives of 130 probands with RLS and compare these rates to those found in a control sample assessed with the same methodology; (2) to test the hypothesis that there is a distinct familial subtype of early-onset RLS and to determine the optimum age of onset for defining such a group; and (3) to deduce the most likely mode of genetic inheritance using segregation analysis of diagnostic data from a projected 1700 family members of our RLS sample, and to perform this analysis separately for early and late onset RLS probands. To date we have studied 87 RLS probands and 39 control probands criteria completed families. We are currently interviewing family members as well as the individual(s) with whom the proband shares biological children. Interviews are being conducted via the telephone using the Validated RLS Structured Diagnostic Telephone Interview. Thus far, we have interviewed 763 eligible and available family members (first and second degree relatives of RLS probands, first degree relatives of control probands, and other parent of proband's children). Of the completed families, 78 total (50 RLS proband families; 28 control proband families), we recruit interviewed family members of RLS and Control probands for blood work, three day activity meter monitoring, and clinical interviews to confirm telephone diagnosis. Seventy-eight families have been completed and analyzed, 50 of whom derive from an RLS proband. Preliminary results show a high frequency of RLS in family members of probands with idiopathic RLS. Furthermore, the frequency of RLS among family members seems to be influenced by age of onset for RLS probands with a higher proportion of relatives affected if the proband had early onset RLS. We have also published the report of the validation of the Johns Hopkins Structured Diagnostic Telephone Interview (TDI) since our last renewal. We conclude that the TDI is a reliable, sensitive and specific instrument for diagnosing RLS when used by experienced interviewers. For the coming year we will continue to identify appropriate probands and interview family members using the TDI. We will maintain collection of blood samples, meter data, and recruitment for the face-to-face clinical interview from the interviewed relatives within completed families. We will be able within the next year to perform a segregation analysis on at least the RLS proband families since we anticipate having 70 to 80 families completed within this period.