HLA-D-region genomic DNA restriction fragments in DRw15 (DR2) familial narcolepsy

Restriction fragment length polymorphism (RFLP) associated with the three human lenkocyte antigen (HLA)-D-region gene-specific cDNA probes (gene-specific DQ alpha, DQ beta and DP beta) was evaluated in two Caucasian families from southwestern Ontario, each with two confirmed narcoleptic siblings. The special feature of the two families is that the affected members are not necessarily DRw15 (previously DR2) positive. In family 1, of the two affected sibs one is DRw15 positive, whereas in family 2 all members including the two affected sibs are DRw15 negative. There is no association between narcolepsy and HLA haplotype in the two families. Further, the polymorphic DNA band patterns generated by a number of restriction enzymes do not show a relationship with the presence or absence of narcolepsy. The probe-specific DNA and patterns however do follow the HLA haplotypes associated with the DQ and DR loci. These results suggest that in DRw15-negative narcolepsy, the DNA patterns are not informative with respect to diagnosing or predicting the presence of narcolepsy. Further, such results argue for genetic heterogeneity in narcolepsy, and the role of DRw15 in the development of the disease could at best be viewed as contributory and not essential.