IGH (MU-SWITCH AND GAMMA-1) REGION RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM IN HUMAN NARCOLEPSY

Predisposition to narcolepsy involves genetic factors both in humans a nd in a canine model of the disorder. In humans, narcolepsy is strongl y associated with HLA DR15 and DQB10602. In Dobermans and Labradors, narcolepsy is transmitted as a single autosomal recessive gene with fu ll penetrance (canarc-1). Canine narcolepsy is not linked with DLA, th e canine equivalent of HLA, but cosegregates with a DNA segment with h igh homology with the mu immunoglobulin heavy-chain (IgH) switch-like region (S-mu). To determine if the IgH locus is involved in genetic pr edisposition to human narcolepsy, restriction fragment length polymorp hisms specific for the IgM and IgG cluster within this locus were stud ied in sporadic cases of the disease, as well as in five families with two or more affected individuals. Comparisons were made between contr ol populations and both familial and sporadic cases and for patients w ith and without HLA-DR15 and DQB10602. RFLP analysis at the S-mu and gamma-1 loci, which cover over 200 kb of 14q32.3, indicates that there is no evidence for any association between the IgH region and human n arcolepsy.