DETERMINING THE GENETICS OF THE RESTLESS LEGS SYNDROME

点击翻译按钮获取中文摘要

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.