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Genetics of narcolepsy.

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.

SUBMITTER: Miyagawa T

PROVIDER: S-EPMC6325123 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genetics of narcolepsy.

Miyagawa Taku T Tokunaga Katsushi K

Human genome variation 20190108

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 ...[more]

PMID: 30652006

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Project description:Study objectives: The objectives of this study was perform the global gene expression profiling aimed at identifying differentially expressed genes in the circulating lympho-monocytes of NRLCP patients affected by Narcolepsy with Cataplexy (NRLCP). Based on the tight association to the HLA-DQB1*0602 haplotype in caucasians, it could be hypotesized an immunological dysregulation underlying the pathogenesis of the disease. Design: 10 NRLCP patients with 10 healthy controls were compared. Total RNA isolated from blood specimens was analyzed using microarray technology followed by statistical data analysis to detect genome-wide differential gene expression between patients and controls. Functional analysis of the genelist was performed in order to interpret the biological significance of the data. Results: 173 genes showed significant (p<0.01) differential expression between the two tested conditions. The biological interpretation allowed to categorize differentially expressed genes into main functional groups including includes genes involved in brain development, which could be possibly regarded as peripheral markers of the disease, along with molecular markers of the NRLCP-related dysmetabolic syndrome and immuregulatory molecules. Moreover a striking correlation within selected HLA haplotypes and HLA gene expression was detected, indicating an allele-specific trend of gene expression for the DQB1, DQA1 and DRB4 genes across all the tested subject, regardless of the disease status. Conclusions: the molecular profile associated to NRLCP suggested that molecular markers of neural, metabolic and immunological dysregulation can be detected in blood of NRLCP patients. Moreover, the allele-specific HLA gene expression could suggest a possible direct role of MHCII as a co-factor in the disease etio-pathogenesis A case-control study was performed comparing 10 narcoleptic patients (both sexes, mean age 50, median age 50) with 10 age- and sex-matched healthy controls

Dataset Information

Genetics of narcolepsy.

Publications

Genetics of narcolepsy.

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