Genetic and familial aspects of narcolepsy

Mignot, Emmanuel

doi:10.1212/wnl.50.2_suppl_1.s16

Cited by 549 publications

(319 citation statements)

References 22 publications

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“…Pollmächer and colleagues highlight that while around 50% of first--degree relatives of narcoleptic patients also share the critical gene variant, few of these individuals develop the disorder, suggesting the importance of other genetic and/or environmental influences in its pathogenesis (Pollmächer et al 1990). Indeed, the majority (around two thirds) of monozygotic twins are discordant for narcolepsy (see Mignot 1998, for a review), underscoring the importance of exogenous factors.…”

Section: Bruxism: Bruxism Is a Movement Disorder Characterised By Teementioning

confidence: 99%

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

Barclay

Gregory

2013

Current Topics in Behavioral Neurosciences

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Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities.Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co--occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia, and emotional/ behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

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Section: Bruxism: Bruxism Is a Movement Disorder Characterised By Teementioning

confidence: 99%

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

Barclay

Gregory

2013

Current Topics in Behavioral Neurosciences

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“…When only cases with cataplexy are considered, 0.05% of the population is affected in the United States (Mignot 1998), a prevalence similar to multiple sclerosis. Diagnosis is generally performed using a 4-5 nap test called the multiple sleep latency test (MSLT).…”

Section: Diagnosis Of Narcolepsymentioning

confidence: 99%

“…Human narcolepsy is a multigenic, environmentally influenced disorder (Mignot 1998). Approximately 25-35% of reported monozygotic twins are concordant for the disorder.…”

Section: Genetic Aspects Of Human Narcolepsymentioning

confidence: 99%

A Commentary on the Neurobiology of the Hypocretin/Orexin System

Mignot¹

2001

Neuropsychopharmacology

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Rarely in the history of medicine has scientific discovery moved so quickly from the report of a neurotransmitter system to a disease pathophysiology (Mignot 2001). In 1998, two groups independently identified the same neuropeptide system and called the molecules "hypocretins" and "orexins" respectively (de Lecea et al. 1998;Sakurai et al. 1998). One of the most striking findings of these initial studies was the discrete localization of hypocretin-containing cells within a very discrete region of the lateral hypothalamus. This led one group to call this peptide system "hypocretin", a term derived from hypo thalamus and se cretin (a weak-and contested-homology with secretin was noted by these authors). The established role of the perifornical region in the regulation of appetite, together with the observation that intracerebroventricular injections of the peptides induced food intake in rats, led the other group to coin the term "orexin" (orexis ϭ appetite) for this system.The discovery in 1999 that canine narcolepsy was caused by mutations in the Hypocretin receptor 2 (Hcrtr2) gene is shifting the research emphasis from appetite control to sleep regulation (Lin et al. 1999). This finding was followed by the observation that hypocretin knockout mice have sleep and behavioral abnormalities reminiscent of narcolepsy (Chemelli et al. 1999). Other studies have indicated dense projections to all monoaminergic cell groups and wake-promoting effects of hypocretins when administered centrally (Hagan et al. 1999). More recently, clinical studies have shown that most patients with narcolepsy have undetectable hypocretins in the CSF and a striking decrease in hypocretin immunoreactivity and transcript levels in the perifornical hypothalamus Thannickal et al. 2000). The most fre- quent cause of human narcolepsy is now known to be hypocretin deficiency, most probably as the result of an autoimmune attack against hypocretin-containing cells. In this commentary, I will briefly review the current knowledge regarding this system, speculate on its possible function in sleep regulation and discuss the potential importance of this system for neuropsychiatry. HYPOCRETIN/OREXINS: NEURONATOMY AND RECEPTOR SYSTEMSThe description of this system has been the object of multiple recent reviews ( Kilduff and Peyron 2000;Sutcliffe and de Lecea 2000;Hungs and Mignot 2001;Overeem et al. 2001;Willie et al. 2001) and will only be briefly outlined. Two biologically active peptides encoded by a single two-exon precursor gene, the preprohypocretin (Hcrt) locus, have been described. The precursor gene contains a signal peptide sequence, followed by a first active peptide, hypocretin-1 (or orexin-A), a second active peptide, hypocretin-2 (or orexin-B) and a C-terminal section of unknown biological activity. Endopeptidic cleavage occurs at typical dibasic residue sequences located between the hypocretin peptides and at the C-terminal of the hypocretin-2 sequence. The hypocretin-1 and hypocretin-2 regions but not the C-terminal region of the precursor ...

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“…The development of the disease seems to involve both environmental and genetic factors. 25 to 31% of monozygotic twins were reported to be concordant for narcolepsy (2).…”

Section: What Is Narcolepsy?mentioning

confidence: 99%

Orexin deficiency and narcolepsy

Sakurai¹

2013

Current Opinion in Neurobiology

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Orexin deficiency results in the sleep disorder narcolepsy in many mammalian species, including mice, dogs, and humans, suggesting that the orexin system is particularly important for normal regulation of sleep/wakefulness states, and especially for maintenance of wakefulness. This review discusses animal models of narcolepsy; the contribution of each orexin receptor subtype to the narcoleptic phenotypes; and the etiology of orexin neuronal death. It also raises the possibility of novel therapies targeting the orexin system for sleep disorders including insomia and narcolepsycataplexy.

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Genetic and familial aspects of narcolepsy

Cited by 549 publications

References 22 publications

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

A Commentary on the Neurobiology of the Hypocretin/Orexin System

Orexin deficiency and narcolepsy

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