alexa Genetic and familial aspects of narcolepsy.
Immunology

Immunology

Journal of Vaccines & Vaccination

Author(s): Mignot E

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Abstract Narcolepsy-cataplexy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep. The development of human narcolepsy involves environmental factors acting on a specific genetic background. The importance of environmental factors is evidenced by the reported 25 to 31\% of monozygotic twins who are concordant for narcolepsy. One of the predisposing genetic factors is located in the MHC DQ region. More than 85\% of all narcoleptic patients with definite cataplexy share a specific HLA allele, HLA DQB1*0602 (most often in combination with HLA DR2), compared with 12 to 38\% of the general population, as evaluated in various ethnic groups. Genetic factors other than HLA are also likely to be involved. Even if genuine multiplex families are rare, 1 to 2\% of the first-degree relatives of narcolepsy patients manifest the disorder, compared with 0.02 to 0.18\% in the general population. Studies using a canine model of narcolepsy illustrate the importance of non-MHC genes in disease predisposition. In this model, narcolepsy is transmitted as a single autosomal recessive trait, canarc-1. In spite of an association with immune-related polymorphisms, narcolepsy does not appear to be a classic autoimmune disease. Other pathophysiologic models involving the microglia and the release of specific cytokines in the CNS may be involved and are being explored. This approach, together with positional cloning studies in humans and canines, should reveal the cause of narcolepsy and open new therapeutic avenues.
This article was published in Neurology and referenced in Journal of Vaccines & Vaccination

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