NARCOLEPSY--HUMAN GENETICS AND HLA CORRELATES

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Narcolepsy is a sleep disorder characterized by excessive somnolence and is, in part, genetically determined. This is evident from the strong association observed between the HLA class II genes (D and DR) and the diagnosis of narcolepsy and also from the increased frequency of narcolepsy in relatives of narcoleptics (1.2%) compared with the population rate of the disorder (approximately 0.1%). In previous work, we have also found this strong HLA-DR2 - narcolepsy association and demonstrated that the association does not extend to the most common sleep disorder characterized by excessive somnolence, sleep apnea. However, it is not clear how narcolepsy is inherited. The specific aims of this project are two-fold: 1) determine the mode of genetic transmission of stringently defined narcolepsy, and test for familial aggregation and, where appropriate, determine the mode of transmission of sleep-related symptoms. Specific symptoms of interest are: excessive sleepiness with a short mean sleep latency on the Multiple Sleep Latency Test, increased number of sleep onset REM sleep periods on Multiple Sleep Latency Testing, shortened latency to nocturnal REM sleep, presence of narcoleptic symptoms of cataplexy, and hypnagogic hallucinations and poor, fragmented sleep. 2) examine the role of HLA, the DRw15(DR2); DQw6(DQw1) haplotype in narcolepsy. 3) to explore the hypothesis that a single non-class II gene in the D region on the short arm of human chromosome 6 is necessary for the development of narcolepsy.