DETERMINING THE GENETICS OF THE RESTLESS LEGS SYNDROME

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。不宁腿综合征（RLS）是一种常见的睡眠障碍，影响约5%的人口。其特征在于肢体（通常是腿部）的痛苦感觉的发作，其通过受影响的肢体的运动而缓解。它通常是渐进的，具有不同的发病年龄，但对老年人来说变得更常见和更令人痛苦。患有严重RLS的个体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。 本研究的具体目的是：（1）采用直接访谈法评估130例RLS先证者的一级和二级亲属中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比率进行比较;（2）检验早发性RLS存在一个独特的家族亚型的假设，并确定界定早发性RLS的最佳发病年龄;和（3）使用来自我们的RLS样本的预计的1700个家庭成员的诊断数据的分离分析来推断最可能的遗传模式，并对早发和晚发RLS先证者分别进行这种分析。 迄今为止，我们已经研究了87个RLS先证者和39个对照先证者标准完成的家庭。我们目前正在采访家庭成员以及与先证者共享亲生子女的个人。访谈是通过电话使用经验证的RLS结构化诊断电话访谈进行的。到目前为止，我们已经采访了763名符合条件的家庭成员（RLS先证者的一级和二级亲属，对照先证者的一级亲属，以及先证者子女的其他父母）。 在完成的78个家庭（50个RLS先证者家庭; 28个对照先证者家庭）中，我们招募了RLS和对照先证者的受访家庭成员进行血液检查，三天活动仪监测和临床访谈以确认电话诊断。78个家庭已完成和分析，其中50人来自RLS先证者。初步结果显示，在特发性RLS先证者的家族成员中，RLS的发生频率很高。此外，家族成员中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。自上次更新以来，我们还发布了约翰霍普金斯结构化诊断电话访谈（TDI）的验证报告。我们的结论是TDI是一个可靠的，敏感的和具体的工具，用于诊断RLS时，由经验丰富的访问者使用。 在未来的一年里，我们将继续确定适当的先证者和采访家庭成员使用TDI。我们将继续收集血液样本、血糖仪数据，并从已完成家庭的受访亲属中招募面对面临床访谈。我们将能够在未来一年内至少对RLS先证者家庭进行分离分析，因为我们预计在此期间将有70至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.