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Conclusion. A much higher percentage of narcolepsy and narcolepsy spectrum disorders was identified in our family study than previous reports. Most of the cases were asymptomatic. The shortened MSL and SOREMPs should be regarded as endophenotypes of narcolepsy. Nocturnal sleep variability was found to be associated with a diagnosis of narcolepsy, daytime shortened MSL and SOREMPs among the relatives. Our data was more concordant with a hypothesis of state boundary control/state instability for narcolepsy. Further molecular genotyping with the incorporation of endophenotype concept should be planned.Introduction. Most familial studies on narcolepsy lacked detailed face-to-face clinical interviews and objective polysomnogram (PSG) and daytime multiple sleep latency test (MSLT) measurements. Our preliminary family study found one relative (2.9%) with narcolepsy and about 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]) The aim of this study was to further explore the familial aggregation and transmission pattern in a larger sample of Hong Kong Chinese narcolepsy, all based on detailed face-to-face interviews and objective measurements.Methods. Thirty-four narcolepsy (with/without cataplexy) patients, one hundred and two relatives of these probands and forty-eight healthy controls were included in the study. All probands, relatives and controls underwent an overnight standard nocturnal PSG and a daytime MSLT on the following day. In addition, each subject also had a detailed clinical interview and completed sleep questionnaires. HLA DQB1*0602 genotyping was performed for 32 probands, 94 relatives and 30 controls.Results. Seven (6.9%) relatives were diagnosed as narcolepsy with cataplexy and 9 (8.8%) relatives were diagnosed as narcolepsy without cataplexy. 39 (38.2%) had narcolepsy spectrum disorder and 47 (46.1%) were considered to be normal. A very strong familial aggregation of narcolepsy, narcolepsy spectrum disorder with associated features of shortened MSL (≤8min) and multiple SOREMPs were found in relatives, but not for sleep related hallucinations and sleep paralysis. Cataplexy seemed to breed true with exclusive but a low percentage of occurrence in the relatives of cataplectic-narcoleptic probands when comparing to the non-cataplectic probands (9% v.s. 0%). A close correlation of HLA-DQB1*0602 with cataplexy was found in both probands and their relatives. The narcoleptic relatives had an excess winter-birth when compared to normal relatives. On the other hand, the first-degree relatives of probands born in other seasons rather than winter had a shorter sleep latency in nocturnal sleep and a shorter mean sleep latency in MSLT. Our data suggested a Mendelian recessive model and multiplicative model for the inheritance of narcolepsy and a Mendelian dominant model for narcolepsy spectrum. Subjective questionnaires were unable in differentiating relatives with narcolepsy spectrum disorder from others. Relatives with narcolepsy reported a high rate of irregular sleep-wake patterns with both variable bedtime and nocturnal sleep duration. This nocturnal sleep variability correlated with daytime shortened MSL and SOREMPs among the relatives. In addition, shortened MSL and SOREMPs should be considered as endophenotypes of narcolepsy as they are the intermediate phenotypes that are heritable, state independent, associated with disease in the population and co-segregated with the disease within families.Chen, Lei.Adviser: Wing Yun Kwok.Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3775.Thesis (Ph.D.)--Chinese University of Hong Kong, 2008.Includes bibliographical references (leaves 59-70).Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.Abstracts in English and Chinese.School code: 1307