HLA-DQB1 genotyping in a family with narcolepsy-cataplexy.
Narcolepsy is a unique model for dysfunction in mechanisms that regulate sleep and wakefulness. The narcolepsy syndrome is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hypnagogic and/or hypnopompic hallucinations and sleep paralysis. The current hypothesis for the etiology of narcolepsy is that it is an autoimmune disorder because of its strong association with the human leukocyte antigen (HLA) system. HLA-DQ alleles are not particularly mutated in narcoleptic patients but they directly influence susceptibility to the disease. DQB10602 homozygote carriers have a two to four times higher risk of developing the disease than heterozygote carriers. In the present study we report a rare multiplex familial case of narcolepsy-cataplexy and show the strong effect of the HLA-DQB10602 allele upon the disease phenotype. In the family studied herein, both the proband and his brother are severely affected and homozygous DQB10602, whereas their sister does not carry the allele and is not affected at all. These data corroborate previous findings proposing DQB10602 homozygous subjects to be far more susceptible to narcolepsy. Insights into the DQB10602 positive family that include homozygous subjects may prove to be an important asset in the investigation of genetic vs. environmental factors predisposing to narcolepsy.
Pedrazzoli
Mario
M
Department of Psychobiology, Universidade Federal de São Paulo, Brazil. pedrazzo@psicobio.epm.br
Pontes
Josy Covan
JC
Peirano
Patricio
P
Tufik
Sergio
S
D000328:Adult; D004198:Disease Susceptibility; D005192:Family Health; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009290:Narcolepsy / Q000134:cerebrospinal fluid / Q000235:genetics*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D000068797:Orexins
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D000068797:Orexins