Narcolepsy-cataplexy in Israeli Jews is associated exclusively with the HLA DR2 haplotype. A study at the serological and genomic level.
Narcolepsy is a very rare disease among Israeli Jews with a frequency of 7/3 X 10(6). An investigation of the association of narcolepsy with the human leukocyte antigen system was conducted in Israeli Jews at the serologic and genomic levels. The human leukocyte antigen class I and class II antigen typing of 7 clinically diagnosed narcoleptics, 3 individuals suffering from sleep disorders other than narcolepsy, and 11 healthy matched controls revealed that all narcoleptic patients (100%) investigated in the present study carried the HLA-DR2 haplotype, whereas patients with other sleep disorders did not. The HLA-B7 and DR2 occurred jointly in 57% (4/7) of the narcoleptic patients, as compared to 2% in randomly selected Israeli healthy controls. Restriction fragment length polymorphism analysis was performed with several restriction enzymes and three cDNA probes for DQ alpha, DQ beta, and DR beta genes on genomic DNAs obtained from narcoleptics and patients with other sleep disorders, matched controls, and 3 homozygous typing cells representing the DR2 subtypes Dw2, Dw12, and DwAZH. The restriction fragment length polymorphism analysis showed that all narcoleptics (7 of 7) shared virtually identical restriction fragment length polymorphisms with one of the homozygous typing cells (GSO), which defines DR2,Dw2. The frequency of the DR2,Dw2 haplotype in the healthy Israeli population is 3.2%. Other non-narcoleptic patients did not share these restriction fragment length polymorphisms. These findings indicate that narcolepsy is associated worldwide with the HLA-DR2,Dw2 haplotype.
D000328:Adult; D002385:Cataplexy / Q000235:genetics; D006970:Disorders of Excessive Somnolence / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D015802:HLA-DR2 Antigen; D006239:Haplotypes; D006801:Humans; D066298:In Vitro Techniques; D007557:Israel; D007585:Jews; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D015802:HLA-DR2 Antigen