Abstract
Narcolepsy is a term that was initially coined by Gélineáu in 1880 and is a chronic neurological sleep disorder that manifests as a difficulty in maintaining wakefulness and sleep for long periods. Currently, narcolepsy is subdivided into two types according to the International Classification of Sleep Disorders, 3rd edition: narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2). NT1 is characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis and is caused by a marked reduction in neurons in the hypothalamus that produce orexin (hypocretin), which is a wakefulness-associated neuropeptide. Except for cataplexy, NT2 exhibits most of the same symptoms as NT1. NT1 is a multifactorial disease, and genetic variations at multiple loci are associated with NT1. Almost all patients with NT1 carry the specific human leukocyte antigen (HLA) allele HLA-DQB1*06:02. Genome-wide association studies have uncovered >10 genomic variations associated with NT1. Rare variants associated with NT1 have also been identified by DNA genome sequencing. NT2 is also a complex disorder, but its underlying genetic architecture is poorly understood. However, several studies have revealed loci that increase susceptibility to NT2. The currently identified loci cannot explain the heritability of narcolepsy (NT1 and NT2). We expect that future genomic research will provide important contributions to our understanding of the genetic basis and pathogenesis of narcolepsy.
Highlights
Introduction Narcolepsy was first described byWestphal in 1877 and named by Gélineáu in 1880
A malfunction of the mechanisms that regulate REM sleep can explain some of the symptoms of narcolepsy
narcolepsy type 1 (NT1) is a typical type of hypersomnia that is characterized by excessive daytime sleepiness, cataplexy, and pathological manifestation of REM sleep, which includes hypnagogic hallucinations, sleep paralysis, or sleep onset REM
Summary
Miyagawa and Tokunaga Human Genome Variation (2019) 6:4 genetic and environmental risk factors. Patients with NT2 have normal orexin A levels and do not exhibit cataplexy[16]. Unlike canine narcolepsy, the patients did not have disease causative variants in the prepro-orexin and orexin receptor genes except for one severe early-onset case. In 1984, Honda and Juji found that all narcoleptic patients with cataplexy carried HLA-DR2 at the serological level[17]. This finding was extended to the HLA genotype level and showed that >90% of East Asians, such as Japanese, Koreans, and Chinese, as well as Europeans with NT1 carried the HLA-DRB1*15:01DQB1*06:02 haplotype[18–21]. A minor proportion of East Asian and European patients carry other DRB1-DQB1*06:02 haplotypes[18].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
