Genetic heterogeneity in narcolepsy

Department of Paediatrics, The University of Western Ontario, London, Ontario, Canada
The Lancet (Impact Factor: 45.22). 04/1990; 335(8691):726-7. DOI: 10.1016/0140-6736(90)90842-S
Source: PubMed
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    ABSTRACT: Identification of genes determining narcolepsy susceptibility is important not only for understanding that disorder but also for possible clues to general sleep-control mechanisms. Studies in humans reveal at least one such gene related to the major histocompatibility complex and in dog an as-yet-unmapped single, autosomal recessive gene canarc-1. Gene markers for canarc-1 were therefore sought by DNA restriction fragment length polymorphisms in our colony of narcoleptic dogs. A human mu-switch immunoglobulin probe and the enzyme Hae III identified a gene cosegregating with canarc-1 in backcrossed animals (logarithm of odds scores: m = 24, Z max = 7.2 at theta = 0%). canarc-1 was also shown not to be tightly linked with the dog major histocompatibility complex (m = 40, Z less than -2 at theta less than 4.8%). These results represent the mapping of a non-major histocompatibility complex narcolepsy gene and strongly suggest involvement of the immune system in the pathophysiology of that disease.
    Full-text · Article · May 1991 · Proceedings of the National Academy of Sciences
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    ABSTRACT: Narcolepsy is characterized by excessive sleepiness and abnormal manifestations of rapid eye movement (REM) sleep. Neurochemical studies of human and canine narcolepsy have demonstrated disturbed monoaminergic and cholinergic function and suggest that deficits of noradrenaline availability in specific brain regions may account for much of its disordered pathophysiology. Genetic susceptibility to narcolepsy is closely linked to a specific region of the major histocompatibility complex on chromosome 6 and an important direction for future research will be to unravel the relationship between this gene region and the neurochemical abnormalities of narcolepsy.
    Preview · Article · Jul 1991 · Trends in Neurosciences
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    ABSTRACT: Narcolepsy is a neurological condition that affects 0.02% to 0.09% of Caucasians, North American blacks, and Japanese populations. It is seen in all races, although the percentage of affected subjects has not been investigated in all continents, and it involves both sexes. It was first described in humans by Gelineau (1880). Narcolepsy is a life-long disease that is characterized by abnormal sleep tendencies, including excessive daytime sleepiness, often disturbed nocturnal sleep, and pathological manifestations of rapid eye movement (REM) sleep. The REM sleep abnormalities include sleep-onset REM periods and the dissociated REM sleep inhibitory processes—cataplexy and sleep paralysis (pathological equivalents of REM sleep atonia). Excessive daytime sleepiness, cataplexy (abrupt loss of motor tone induced by emotions) and, less often, sleep paralysis and hypnagogic hallucinations are the major symptoms of the disease. The causes of human narcolepsy are currently unknown but may involve a defect of the specific mechanisms regulating REM sleep and wakefulness.
    No preview · Chapter · Jan 1992
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